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Park JY, Jang M, Lee SM, Woo J, Lee EJ, Kim D. Unveiling the novel regulatory roles of RpoD-family sigma factors in Salmonella Typhimurium heat shock response through systems biology approaches. PLoS Genet 2024; 20:e1011464. [PMID: 39471211 PMCID: PMC11548764 DOI: 10.1371/journal.pgen.1011464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/08/2024] [Accepted: 10/18/2024] [Indexed: 11/01/2024] Open
Abstract
Three RpoD-family sigma factors, RpoD, RpoS, and RpoH, play critical roles in transcriptional regulation in Salmonella enterica serovar Typhimurium under heat shock conditions. However, the genome-wide regulatory mechanisms of these sigma factors in response to heat stress have remained elusive. In this study, we comprehensively identified 2,319, 2,226, and 213 genome-wide binding sites for RpoD, RpoS, and RpoH, respectively, under sublethal heat shock conditions (42°C). Machine learning-based transcriptome analysis was employed to infer the relative activity of iModulons, providing valuable insights into the transcriptional impact of heat shock. Integrative data analysis enabled the reconstruction of the transcriptional regulatory network of sigma factors, revealing how they modulate gene expression to adapt to heat stress, including responses to anaerobic and oxidative stresses. Notably, we observed a significant expansion of the RpoS sigmulon from 97 to 301 genes in response to heat shock, underscoring the crucial role of RpoS in regulating various metabolic processes. Moreover, we uncovered a competition mechanism between RpoD and RpoS within RpoS sigmulons, where RpoS significantly increases its binding within promoter regions shared with RpoD under heat shock conditions. These findings illuminate how three RpoD-family sigma factors coordinate multiple cellular processes to orchestrate the overall response of S. Typhimurium to heat stress.
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Affiliation(s)
- Joon Young Park
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Minchang Jang
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Sang-Mok Lee
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Jihoon Woo
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Eun-Jin Lee
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Donghyuk Kim
- School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
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Ayyadurai VAS, Deonikar P, Fields C. Mechanistic Understanding of D-Glucaric Acid to Support Liver Detoxification Essential to Muscle Health Using a Computational Systems Biology Approach. Nutrients 2023; 15:733. [PMID: 36771439 PMCID: PMC9921405 DOI: 10.3390/nu15030733] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/10/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
Liver and muscle health are intimately connected. Nutritional strategies that support liver detoxification are beneficial to muscle recovery. Computational-in silico-molecular systems' biology analysis of supplementation of calcium and potassium glucarate salts and their metabolite D-glucaric acid (GA) reveals their positive effect on mitigation of liver detoxification via four specific molecular pathways: (1) ROS production, (2) deconjugation, (3) apoptosis of hepatocytes, and (4) β-glucuronidase synthesis. GA improves liver detoxification by downregulating hepatocyte apoptosis, reducing glucuronide deconjugates levels, reducing ROS production, and inhibiting β-Glucuronidase enzyme that reduces re-absorption of toxins in hepatocytes. Results from this in silico study provide an integrative molecular mechanistic systems explanation for the mitigation of liver toxicity by GA.
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Affiliation(s)
- V. A. Shiva Ayyadurai
- Systems Biology Group, CytoSolve Research Division, CytoSolve, Inc., Cambridge, MA 02138, USA
| | - Prabhakar Deonikar
- Systems Biology Group, CytoSolve Research Division, CytoSolve, Inc., Cambridge, MA 02138, USA
| | - Christine Fields
- Applied Food Sciences Inc., 8708 South Congress Suite 290, Austin, TX 78745, USA
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3
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Lament K, Nieszporek J, Piasecki W. Electrochemical Analysis of Fe 2+ Ions Behavior in the Metal Oxide Dispersions. BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 2022. [DOI: 10.1246/bcsj.20220189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Karolina Lament
- Regional Research and Development Center, Józef Piłsudski University of Physical Education in Warsaw, Akademicka 2, 21-500 Biała Podlaska, Poland
| | - Jolanta Nieszporek
- Department of Analytical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, M. Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland
| | - Wojciech Piasecki
- Faculty of Physical Education and Health, Józef Piłsudski University of Physical Education in Warsaw, Akademicka 2, 21-500 Biała Podlaska, Poland
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4
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Razavi M, Barras A, Ifires M, Swaidan A, Khoshkam M, Szunerits S, Kompany-Zareh M, Boukherroub R. Colorimetric assay for the detection of dopamine using bismuth ferrite oxide (Bi 2Fe 4O 9) nanoparticles as an efficient peroxidase-mimic nanozyme. J Colloid Interface Sci 2022; 613:384-395. [PMID: 35042036 DOI: 10.1016/j.jcis.2022.01.041] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/03/2022] [Accepted: 01/06/2022] [Indexed: 10/19/2022]
Abstract
This work describes the preparation of ternary bismuth ferrite oxide nanoparticles (Bi2Fe4O9 NPs) with an enzyme mimetic activity for dopamine (DA) qualitative and quantitative detection. Bi2Fe4O9 NPs were prepared using a facile, low cost, and one-pot hydrothermal treatment. The chemical composition, morphology, and optical properties of Bi2Fe4O9 nanozyme were characterized using different techniques such as Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction pattern (XRD), X-ray photoelectron spectroscopy (XPS), thermo-gravimetric analysis (TGA), dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM) imaging, FESEM-energy dispersive X-ray spectroscopy (EDS), UV-vis absorption, and fluorescence emission spectroscopy. Bi2Fe4O9 NPs were utilized to catalyze the oxidation of a typical chromogenic peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), to form the blue-colored oxidized product (oxTMB), in the presence of hydrogen peroxide (H2O2). All reactions occurred in acetate buffer solution (pH 3.5) to generate hydroxyl radicals (•OH) and the kinetics were followed by UV-vis absorbance at 654 nm. The steady-state kinetic parameters were obtained from the Michaelis-Menten equation and exhibited a good catalytic efficiency of Bi2Fe4O9 NPs as enzyme mimetics. Michaelis-Menten constant (Km) values were estimated as 0.07 and 0.73 mM for TMB and H2O2, respectively. The presented method is efficient, rapid, cost-effective, and sensitive for the colorimetric detection of dopamine with a linear range (LR) from 0.15 to 50 μM and a detection limit (LOD) of 51 nM. The proposed colorimetric sensor was successfully applied for the detection of different concentrations of dopamine in spiked fetal bovine serum (FBS) and horse serum (HS) samples. It is anticipated that Bi2Fe4O9 nanozyme holds great potential in biomedical analysis and diagnostic applications of dopamine-related diseases.
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Affiliation(s)
- Mehri Razavi
- Department of Chemistry, Institute for Advanced Studies in Basic Sciences, Zanjan 45137-66731, Iran; Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France
| | - Alexandre Barras
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France
| | - Madjid Ifires
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France; Research Center of Semi-conductor Technology for Energy, CRTSE - 02, Bd. Dr. Frantz FANON, B.P. 140 Algiers-7, Merveilles 16038, Algeria
| | - Abir Swaidan
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France
| | - Maryam Khoshkam
- Department of Chemistry, Faculty of Science, Mohaghegh Ardabili University, 56199-11367, Ardabil, Iran
| | - Sabine Szunerits
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France
| | - Mohsen Kompany-Zareh
- Department of Chemistry, Institute for Advanced Studies in Basic Sciences, Zanjan 45137-66731, Iran; Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. Box 15000, Halifax, NS B3H 4R2, Canada
| | - Rabah Boukherroub
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, Lille F-59000, France.
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5
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Grassmann AA, Zavala-Alvarado C, Bettin EB, Picardeau M, Benaroudj N, Caimano MJ. The FUR-like regulators PerRA and PerRB integrate a complex regulatory network that promotes mammalian host-adaptation and virulence of Leptospira interrogans. PLoS Pathog 2021; 17:e1009078. [PMID: 34855918 PMCID: PMC8638967 DOI: 10.1371/journal.ppat.1009078] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 02/18/2021] [Indexed: 11/18/2022] Open
Abstract
Leptospira interrogans, the causative agent of most cases of human leptospirosis, must respond to myriad environmental signals during its free-living and pathogenic lifestyles. Previously, we compared L. interrogans cultivated in vitro and in vivo using a dialysis membrane chamber (DMC) peritoneal implant model. From these studies emerged the importance of genes encoding the Peroxide responsive regulators PerRA and PerRB. First described in in Bacillus subtilis, PerRs are widespread in Gram-negative and -positive bacteria, where regulate the expression of gene products involved in detoxification of reactive oxygen species and virulence. Using perRA and perRB single and double mutants, we establish that L. interrogans requires at least one functional PerR for infectivity and renal colonization in a reservoir host. Our finding that the perRA/B double mutant survives at wild-type levels in DMCs is noteworthy as it demonstrates that the loss of virulence is not due to a metabolic lesion (i.e., metal starvation) but instead reflects dysregulation of virulence-related gene products. Comparative RNA-Seq analyses of perRA, perRB and perRA/B mutants cultivated within DMCs identified 106 genes that are dysregulated in the double mutant, including ligA, ligB and lvrA/B sensory histidine kinases. Decreased expression of LigA and LigB in the perRA/B mutant was not due to loss of LvrAB signaling. The majority of genes in the perRA and perRB single and double mutant DMC regulons were differentially expressed only in vivo, highlighting the importance of host signals for regulating gene expression in L. interrogans. Importantly, the PerRA, PerRB and PerRA/B DMC regulons each contain multiple genes related to environmental sensing and/or transcriptional regulation. Collectively, our data suggest that PerRA and PerRB are part of a complex regulatory network that promotes host adaptation by L. interrogans within mammals.
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Affiliation(s)
- André A. Grassmann
- Department of Medicine, University of Connecticut Health, Farmington, Connecticut, United States of America
| | - Crispin Zavala-Alvarado
- Unité de Biologie des Spirochètes, Department of Microbiology, Institut Pasteur, Paris, France
- Université de Paris, Sorbonne Paris Cité, Communauté d’universités et d’établissements (COMUE), Bio Sorbonne Paris Cité (BioSPC), Paris, France
| | - Everton B. Bettin
- Department of Medicine, University of Connecticut Health, Farmington, Connecticut, United States of America
- Programa de Pós-Graduação em Biotecnologia, Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sol, Brazil
| | - Mathieu Picardeau
- Unité de Biologie des Spirochètes, Department of Microbiology, Institut Pasteur, Paris, France
| | - Nadia Benaroudj
- Unité de Biologie des Spirochètes, Department of Microbiology, Institut Pasteur, Paris, France
| | - Melissa J. Caimano
- Department of Medicine, University of Connecticut Health, Farmington, Connecticut, United States of America
- Department of Pediatrics, University of Connecticut Health, Farmington, Connecticut, United States of America
- Department of Molecular Biology and Biophysics, University of Connecticut Health, Farmington, Connecticut, United States of America
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Yao Y, Xue M, Mao W, Li Y, Zhu A, Chen T, Shen W, Liu C, Chen L, Tang S. Ni/Fe layered double hydroxide nanosheet/G-quadruplex as a new complex DNAzyme with highly enhanced peroxidase-mimic activity. Analyst 2021; 146:6470-6473. [PMID: 34609387 DOI: 10.1039/d1an01405f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
A novel and low-cost DNAzyme, Ni/Fe layered double hydroxide (LDH) nanosheet/G-quadruplex (without hemin) with enhanced peroxidase-mimic activity was designed. The catalytic mechanism was investigated. The detection of Cu(II) in actual serum samples could be realized sensitively via this efficient DNAzyme-based method.
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Affiliation(s)
- Yao Yao
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Mingliang Xue
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Wei Mao
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Yana Li
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Anni Zhu
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Tianyu Chen
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Wei Shen
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Chang Liu
- School of Grain Science and Technology, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Lizhuang Chen
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
| | - Sheng Tang
- School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu Province, PR China.
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7
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Chen HY, Lin YF. DFT mechanistic study on the formation of 8-oxoguanine and spiroiminodihydantoin mediated by iron Fenton reactions. Dalton Trans 2021; 50:9842-9850. [PMID: 34190261 DOI: 10.1039/d1dt01508g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Fenton reactions unavoidably take place in the human body and have been demonstrated to cause oxidative DNA damage. However, the molecular-level understanding of DNA damage mediated by Fenton reactions is limited. Herein, density functional theory (DFT) calculations were made to investigate the counterion effects on aqueous Fenton reactions and the detailed mechanisms of chemical modifications to guanine induced by Fenton reactions. Our calculations show that the activation energy of the Fenton reaction catalyzed by a pure aquo complex [FeII(H2O)6]2+ is too high to agree with experiments, whereas complexation with counteranions reduces the activation energy to a reasonable range. This result suggests that FeII-counteranion complexes are the real catalyst for fast aqueous Fenton reactions. In addition, we found that the Fenton oxidation mediated by FeII bonded to the N7 atom of guanine can result in the formation of 8-oxoguanine and spiroiminodihydantoin through multiple reaction pathways, including the electrophilic addition of ˙OH, H-abstraction by ˙OH, and oxygen atom transfer of oxoiron(iv) species. The activation of hydrogen peroxide by ferrous iron is the rate-determining step. The guanine N7-bound iron ion and the coordinated counteranion were found to play an important role in the Fenton oxidation of guanine.
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Affiliation(s)
- Hsing-Yin Chen
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Yu-Fen Lin
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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8
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Gao C, Yao M, Li S, Feng P, Peng S, Shuai C. Highly biodegradable and bioactive Fe-Pd-bredigite biocomposites prepared by selective laser melting. J Adv Res 2019; 20:91-104. [PMID: 31304046 PMCID: PMC6603336 DOI: 10.1016/j.jare.2019.06.001] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/06/2019] [Accepted: 06/17/2019] [Indexed: 12/11/2022] Open
Abstract
Iron (Fe) has been highly anticipated as a bone implant material owing to the biodegradability and excellent mechanical properties, but limited by the slow degradation and poor bioactivity. In this study, novel Fe-palladium (Pd)-bredigite biocomposites were developed by selective laser melting aiming to improve both the degradation behavior and bioactivity of Fe. The results showed that most Pd formed Pd-rich intermetallic phases (IMPs) with a nearly continuous network while the bredigite phase was distributed at the grain boundaries. In addition, a large amount of much nobler IMPs formed micro-galvanic pairs with the Fe matrix, inducing tremendous micro-galvanic corrosion. The IMPs contained a high amount of Pd2+ with a high reduction potential, which further promoted the efficiency of micro-galvanic corrosion. Moreover, the rapid degradation of bredigite also facilitated the penetration of the corrosion medium. As a result, the Fe-4Pd-5bredigite biocomposite showed a uniform degradation with a rate that is 6 times that of Fe. Furthermore, the developed Fe-Pd-bredigite biocomposites also featured excellent bioactivity, cytocompatibility, and suitable mechanical properties as characterized by the rapid apatite deposition, normal proliferation of human osteoblast-like cells (MG-63), and comparable strength and microhardness with the native bone. Overall, this study opens a new avenue for improving both the degradation and bioactivity of Fe-based composites and may facilitate their applications as biodegradable implants for tissue/organ repair.
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Affiliation(s)
- Chengde Gao
- State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China
| | - Meng Yao
- State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China
| | - Sheng Li
- State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China
| | - Pei Feng
- State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China
| | - Shuping Peng
- NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410013, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha 410013, China
| | - Cijun Shuai
- State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China
- Jiangxi University of Science and Technology, Ganzhou 341000, China
- Shenzhen Institute of Information Technology, Shenzhen 518172, China
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9
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Qian W, Kumar N, Roginskaya V, Fouquerel E, Opresko PL, Shiva S, Watkins SC, Kolodieznyi D, Bruchez MP, Van Houten B. Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction. Proc Natl Acad Sci U S A 2019; 116:18435-18444. [PMID: 31451640 PMCID: PMC6744920 DOI: 10.1073/pnas.1910574116] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Reactive oxygen species (ROS) play important roles in aging, inflammation, and cancer. Mitochondria are an important source of ROS; however, the spatiotemporal ROS events underlying oxidative cellular damage from dysfunctional mitochondria remain unresolved. To this end, we have developed and validated a chemoptogenetic approach that uses a mitochondrially targeted fluorogen-activating peptide (Mito-FAP) to deliver a photosensitizer MG-2I dye exclusively to this organelle. Light-mediated activation (660 nm) of the Mito-FAP-MG-2I complex led to a rapid loss of mitochondrial respiration, decreased electron transport chain complex activity, and mitochondrial fragmentation. Importantly, one round of singlet oxygen produced a persistent secondary wave of mitochondrial superoxide and hydrogen peroxide lasting for over 48 h after the initial insult. By following ROS intermediates, we were able to detect hydrogen peroxide in the nucleus through ratiometric analysis of the oxidation of nuclear cysteine residues. Despite mitochondrial DNA (mtDNA) damage and nuclear oxidative stress induced by dysfunctional mitochondria, there was a lack of gross nuclear DNA strand breaks and apoptosis. Targeted telomere analysis revealed fragile telomeres and telomere loss as well as 53BP1-positive telomere dysfunction-induced foci (TIFs), indicating that DNA double-strand breaks occurred exclusively in telomeres as a direct consequence of mitochondrial dysfunction. These telomere defects activated ataxia-telangiectasia mutated (ATM)-mediated DNA damage repair signaling. Furthermore, ATM inhibition exacerbated the Mito-FAP-induced mitochondrial dysfunction and sensitized cells to apoptotic cell death. This profound sensitivity of telomeres through hydrogen peroxide induced by dysregulated mitochondria reveals a crucial mechanism of telomere-mitochondria communication underlying the pathophysiological role of mitochondrial ROS in human diseases.
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Affiliation(s)
- Wei Qian
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
| | - Namrata Kumar
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- Molecular Genetics and Developmental Biology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
| | - Vera Roginskaya
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
| | - Elise Fouquerel
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261
| | - Patricia L Opresko
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261
| | - Sruti Shiva
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
| | - Simon C Watkins
- Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261
- Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261
| | - Dmytro Kolodieznyi
- Department of Chemistry, Molecular Biosensors and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213
| | - Marcel P Bruchez
- Department of Chemistry, Molecular Biosensors and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213
- Department of Biological Sciences, and Molecular Biosensors and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213
| | - Bennett Van Houten
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;
- University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
- Molecular Genetics and Developmental Biology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
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10
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Pal Singh P, Vithalapuram V, Metre S, Kodipyaka R. Lipoplex-based therapeutics for effective oligonucleotide delivery: a compendious review. J Liposome Res 2019; 30:313-335. [DOI: 10.1080/08982104.2019.1652645] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Pirthi Pal Singh
- Department of Formulation Research and Development, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Hyderabad, India
| | - Veena Vithalapuram
- Department of Formulation Research and Development, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Hyderabad, India
| | - Sunita Metre
- Department of Formulation Research and Development, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Hyderabad, India
| | - Ravinder Kodipyaka
- Department of Formulation Research and Development, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Hyderabad, India
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11
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Lian TH, Guo P, Zuo LJ, Hu Y, Yu SY, Yu QJ, Jin Z, Wang RD, Li LX, Zhang W. Tremor-Dominant in Parkinson Disease: The Relevance to Iron Metabolism and Inflammation. Front Neurosci 2019; 13:255. [PMID: 30971879 PMCID: PMC6445850 DOI: 10.3389/fnins.2019.00255] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 03/04/2019] [Indexed: 12/11/2022] Open
Abstract
Background: Tremor is one of the most predominant symptoms of patients with Parkinson disease (PD), but the underlying mechanisms for tremor relating to iron and its metabolism-related proteins and the inflammatory factors in cerebrospinal fluid (CSF) and serum have not been fully elucidated. Methods: A total of 135 PD patients were divided into a tremor-dominant (PD-TD) group (N = 74) and a postural instability and gait difficulty-dominant (PD-PIGD) group (N = 39) based on the ratio of mean tremor score to the mean bradykinesia/rigid score of the Unified Parkinson's Disease Rating Scale (UPDRS) III. Age and sex-matched healthy controls were recruited (N = 35). Demographic variables were evaluated; iron and its metabolism-related proteins and the inflammatory mediators in both CSF and serum were measured in these groups. The relevance of iron metabolism, inflammation and PD-TD were analyzed. Results: (1) The PD-TD group had significantly decreased L-ferritin, increased iron levels in CSF and increased ferritin levels in the serum compared with the PD-PIGD and control groups (P < 0.05). (2) The PD-TD group had significantly enhanced IL-6 levels in both CSF and serum compared with the PD-PIGD and control groups (P < 0.05). (3) In CSF, the IL-6 level was increased as the iron level was elevated in the PD-TD group (r = 0.308, P = 0.022). In serum, the IL-6 level was increased as the ferritin level was elevated in the PD-TD group (r = 0.410, P = 0.004). Conclusion: The interplay between disturbed iron metabolism and relevant inflammation might modulate clinical phenotypes of PD.
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Affiliation(s)
- Teng-Hong Lian
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Peng Guo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Li-Jun Zuo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yang Hu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shu-Yang Yu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Qiu-Jin Yu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Zhao Jin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Rui-Dan Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Li-Xia Li
- Department of Internal Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wei Zhang
- Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, China
- Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory on Parkinson’s Disease, Beijing, China
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12
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Namvar F, Sadat Sangsefidi F, Salavati-Niasari M. Tb 2MoO 6 nanostructure: Ultrasonic controlling the size and morphology, characterization and investigation of its photo-catalytic activity for dyes as the water pollutants under UV light illumination. JOURNAL OF HAZARDOUS MATERIALS 2018; 360:288-302. [PMID: 30125745 DOI: 10.1016/j.jhazmat.2018.08.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 08/07/2018] [Accepted: 08/09/2018] [Indexed: 06/08/2023]
Abstract
For the first time, pure Tb2MoO6 nanostructures were successfully fabricated using Tb(NO3)3.6H2O and (NH4)6Mo7O24.4H2O as a precursor by ultrasonic method and characterized by via X-ray powder diffraction (XRD), Fourier-transformed infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and Energy-dispersive X-ray spectroscopy (EDS). The various parameters such as the type of capping agent, ultrasonic time and power were optimized to achieve the appropriate sample. The results showed that the type of capping agent, ultrasonic time and power can influence on the morphology, size, and purity of the products, respectively. In this work, pure Tb2MoO6 nanostructures observed by PVP as capping agent in ultrasonic time and power of 30 min and 80 W, respectively. Optical property of optimized product was investigated via diffuse reflectance spectroscopy (DRS). The photo-catalytic activity of proposed nanostructure was studied in the presence of various dyes such as Methylene blue, methyl orange, and acid blue 92 as the water pollutants under UV light illumination. At 0.05 g of nanostructure, Methyl orange pollutant destruction was higher than the two other dyes.
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Affiliation(s)
- Farzad Namvar
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167, Iran
| | | | - Masoud Salavati-Niasari
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167, Iran.
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13
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Sun J, Li Y, Chen C, Qi T, Xia D, Mao W, Yang T, Chen L, Shen W, Tang S. Magnetic Ni/Fe layered double hydroxide nanosheets as enhancer for DNA hairpin sensitive detection of miRNA. Talanta 2018; 187:265-271. [DOI: 10.1016/j.talanta.2018.05.037] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 04/02/2018] [Accepted: 05/08/2018] [Indexed: 11/16/2022]
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14
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Kocaman A, Altun G, Kaplan AA, Deniz ÖG, Yurt KK, Kaplan S. Genotoxic and carcinogenic effects of non-ionizing electromagnetic fields. ENVIRONMENTAL RESEARCH 2018; 163:71-79. [PMID: 29427953 DOI: 10.1016/j.envres.2018.01.034] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 01/14/2018] [Accepted: 01/23/2018] [Indexed: 05/06/2023]
Abstract
New technologies in electronics and communications are continually emerging. An increasing use of these electronic devices such as mobile phone, computer, wireless fidelity connectors or cellular towers is raising questions concerning whether they have an adverse effect on the body. Exposure to electromagnetic fields (EMF) is frequently suggested to have adverse health effects on humans and other organisms. This idea has been reported in many studies. In contrast, the therapeutic effects of EMF on different organs have also been reported. Research findings are inconsistent. This has given rise to very profound discrepancies. The duration and frequency of mobile phone calls and the association observed with various health effects has raised serious concerns due to the frequency with which these devices are used and the way they are held close to the head. The present review assesses the results of in vitro, in vivo, experimental, and epidemiological studies. The purpose of the study is to assess data concerning the carcinogenic and genotoxic effects of non-ionizing EMF. The major genotoxic and carcinogenic effects of EMF, divided into subsections as low frequency effects and radiofrequency effects, were reviewed. The inconsistent results between similar studies and the same research groups have made it very difficult to make any comprehensive interpretation. However, evaluation of current studies suggests that EMF may represent a serious source of concern and may be hazardous to living organisms.
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Affiliation(s)
- Adem Kocaman
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey.
| | - Gamze Altun
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey
| | - Arife Ahsen Kaplan
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey
| | - Ömür Gülsüm Deniz
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey
| | - Kıymet Kübra Yurt
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey
| | - Süleyman Kaplan
- Department of Histology and Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey
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15
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Mahdiani M, Soofivand F, Salavati-Niasari M. Investigation of experimental and instrumental parameters on properties of PbFe 12O 19 nanostructures prepared by sonochemical method. ULTRASONICS SONOCHEMISTRY 2018; 40:271-281. [PMID: 28946425 DOI: 10.1016/j.ultsonch.2017.06.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 06/24/2017] [Accepted: 06/25/2017] [Indexed: 06/07/2023]
Abstract
It is the first time that PbFe12O19 nanostructures were successfully synthesized by sonochemical method. The instrumental and experimental parameters were optimized to achieve the appropriate product. The results showed that Pb+2 to Fe+3 molar ratio and the type of capping agent as experimental parameters and time and power of sonication as instrumental variables can influence on the purity and particle size of products, respectively. According to the results, the synthesis process could improve to sol-gel assisted sonochemical method in presence of PEG as capping agent. In this method, pure product obtained by using the high temperature and pressure in sonication treatment and hydrolysis and condensation processes in sol-gel method, simultaneously. Concurrent presence of sonication treatment and PEG were necessary for preparation of pure hexaferrite nanostructures. Because of metal oxides nanostructures as major product and hexaferrite as minor product were produced in the absence of them. So, sol-gel assisted sonochemical method can be introduced as an effective method for preparation of hexaferrite nanostructures. Furthermore, it was found that the instrumental parameters should be optimized, because of increasing the time and power of sonication is not always favorable for preparation of ultrafine particles and small structures.
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Affiliation(s)
- Maryam Mahdiani
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box. 87317-51167, Iran
| | - Faezeh Soofivand
- Young Researchers and Elite Club, Bandar Abbas Branch, Islamic Azad University, Bandar Abbas, Iran
| | - Masoud Salavati-Niasari
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box. 87317-51167, Iran.
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16
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Wang C, Wang Q, Tan R. Preparation of enzyme-functionalized carbon nanotubes and their application in glucose and Fe2+ detection through “turn on” and “turn off” approaches. Analyst 2018; 143:4118-4127. [DOI: 10.1039/c8an00823j] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Herein, we report the preparation of enzyme-conjugated carbon nanotubes for the detection of Fe2+ and glucose with enhanced signal intensity.
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Affiliation(s)
- Chengke Wang
- College of Food and Biological Engineering
- Jiangsu University
- Zhenjiang 212013
- P. R. China
| | - Qingqing Wang
- College of Food and Biological Engineering
- Jiangsu University
- Zhenjiang 212013
- P. R. China
| | - Rong Tan
- College of Food and Biological Engineering
- Jiangsu University
- Zhenjiang 212013
- P. R. China
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17
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Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance. Sci Rep 2017; 7:14973. [PMID: 29097764 PMCID: PMC5668412 DOI: 10.1038/s41598-017-14721-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 10/17/2017] [Indexed: 11/08/2022] Open
Abstract
Parkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.
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Kar I, Chattopadhyaya R. Effect of seven Indian plant extracts on Fenton reaction-mediated damage to DNA constituents. J Biomol Struct Dyn 2016; 35:2997-3011. [PMID: 27691720 DOI: 10.1080/07391102.2016.1244493] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The influences of substoichiometric amounts of seven plant extracts in the Fenton reaction-mediated damage to deoxynucleosides, deoxynucleoside monophosphates, deoxynucleoside triphosphates, and supercoiled plasmid DNA were studied to rationalize anticancer properties reported in some of these extracts. Extracts from Acacia catechu, Emblica officinalis, Spondias dulcis, Terminalia belerica, Terminalia chebula, as well as gallic acid, epicatechin, chebulagic acid and chebulinic acid enhance the extent of damage in Fenton reactions with all monomeric substrates but protect supercoiled plasmid DNA, compared to standard Fenton reactions. The damage to pyrimidine nucleosides/nucleotides is enhanced by these extracts and compounds to a greater extent than for purine ones in a concentration dependent manner. Dolichos biflorus and Hemidesmus indicus extracts generally do not show this enhancement for the monomeric substrates though they protect plasmid DNA. Compared to standard Fenton reactions for deoxynucleosides with ethanol, the presence of these five plant extracts render ethanol scavenging less effective as the radical is generated in the vicinity of the target. Since substoichiometric amounts of these extracts and the four compounds produce this effect, a catalytic mechanism involving the presence of a ternary complex of the nucleoside/nucleotide substrate, a plant compound and the hydroxyl radical is proposed. Such a mechanism cannot operate for plasmid DNA as the planar rings in the extract compounds cannot stack with the duplex DNA bases. These plant extracts, by enhancing Fenton reaction-mediated damage to deoxynucleoside triphosphates, slow down DNA replication in rapidly dividing cancer cells, thus contributing to their anticancer properties.
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Affiliation(s)
- Indrani Kar
- a Department of Biochemistry , Bose Institute , P-1/12, C. I. T. Scheme VIIM, Kolkata 700054 , India
| | - Rajagopal Chattopadhyaya
- a Department of Biochemistry , Bose Institute , P-1/12, C. I. T. Scheme VIIM, Kolkata 700054 , India
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19
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Shiva Ayyadurai VA, Hansen M, Fagan J, Deonikar P. <i>In-Silico</i> Analysis & <i>In-Vivo</i> Results Concur on Glutathione Depletion in Glyphosate Resistant GMO Soy, Advancing a Systems Biology Framework for Safety Assessment of GMOs. ACTA ACUST UNITED AC 2016. [DOI: 10.4236/ajps.2016.712149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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20
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Shokolenko IN, Wilson GL, Alexeyev MF. Aging: A mitochondrial DNA perspective, critical analysis and an update. World J Exp Med 2014; 4:46-57. [PMID: 25414817 PMCID: PMC4237642 DOI: 10.5493/wjem.v4.i4.46] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 07/15/2014] [Accepted: 08/31/2014] [Indexed: 02/06/2023] Open
Abstract
The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA (mtDNA) damage by reactive oxygen species (ROS) as its cornerstone, has been increasingly losing ground and is undergoing extensive revision due to its inability to explain a growing body of emerging data. Concurrently, the notion of the central role for mtDNA in the aging process is being met with increased skepticism. Our progress in understanding the processes of mtDNA maintenance, repair, damage, and degradation in response to damage has largely refuted the view of mtDNA as being particularly susceptible to ROS-mediated mutagenesis due to its lack of “protective” histones and reduced complement of available DNA repair pathways. Recent research on mitochondrial ROS production has led to the appreciation that mitochondria, even in vitro, produce much less ROS than previously thought, automatically leading to a decreased expectation of physiologically achievable levels of mtDNA damage. New evidence suggests that both experimentally induced oxidative stress and radiation therapy result in very low levels of mtDNA mutagenesis. Recent advances provide evidence against the existence of the “vicious” cycle of mtDNA damage and ROS production. Meta-studies reveal no longevity benefit of increased antioxidant defenses. Simultaneously, exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity. A novel paradigm suggests that increased ROS production in aging may be the result of adaptive signaling rather than a detrimental byproduct of normal respiration that drives aging. Here, we review issues pertaining to the role of mtDNA in aging.
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21
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Morris G, Robertson I, Tatko CD. Iron binding β-hairpin peptides. Biometals 2013; 26:667-75. [DOI: 10.1007/s10534-013-9638-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 05/26/2013] [Indexed: 10/26/2022]
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22
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Alexeyev M, Shokolenko I, Wilson G, LeDoux S. The maintenance of mitochondrial DNA integrity--critical analysis and update. Cold Spring Harb Perspect Biol 2013; 5:a012641. [PMID: 23637283 DOI: 10.1101/cshperspect.a012641] [Citation(s) in RCA: 306] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
DNA molecules in mitochondria, just like those in the nucleus of eukaryotic cells, are constantly damaged by noxious agents. Eukaryotic cells have developed efficient mechanisms to deal with this assault. The process of DNA repair in mitochondria, initially believed nonexistent, has now evolved into a mature area of research. In recent years, it has become increasingly appreciated that mitochondria possess many of the same DNA repair pathways that the nucleus does. Moreover, a unique pathway that is enabled by high redundancy of the mitochondrial DNA and allows for the disposal of damaged DNA molecules operates in this organelle. In this review, we attempt to present a unified view of our current understanding of the process of DNA repair in mitochondria with an emphasis on issues that appear controversial.
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Affiliation(s)
- Mikhail Alexeyev
- Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, AL 36688, USA
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23
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Chattopadhyaya R. Oxidative damage to DNA constituents by iron-mediated Fenton reactions – the thymidine family. J Biomol Struct Dyn 2012; 32:155-69. [DOI: 10.1080/07391102.2012.745167] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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24
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Life in the serendipitous lane: excitement and gratification in studying DNA repair. DNA Repair (Amst) 2012; 11:595-605. [PMID: 22870513 DOI: 10.1016/j.dnarep.2011.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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25
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Chattopadhyaya R, Goswami B. Oxidative damage to DNA constituents by iron-mediated Fenton reactions: the deoxyadenosine family. J Biomol Struct Dyn 2012; 30:394-406. [PMID: 22686514 DOI: 10.1080/07391102.2012.682206] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
The effect of exposing 2'-deoxyadenosine (dA), 5'-dAMP, 3'-dAMP, dApA, dA(pdA)(19,) and poly(dA): oligo(dT) to iron/H(2)O(2) in the presence and absence of ethanol or NADH has been studied. HPLC retention times, enzyme treatments, radio-labeled substrates, UV absorption spectra, and fast atom bombardment mass spectrometry (FABMS) have been used to distinguish 20 products arising from the reaction, of which 16 have been identified and four anomers proposed by comparison with earlier gamma radiation studies. The radical responsible for the reactions seems to be analogous to radiation-derived [Formula: see text], has many products in common, but has some novel ones probably specific for Fenton-induced damage. Two new dimeric adducts arising from the generation of hydroxylamine at N7 and its subsequent condensation with two known sugar damage products, dR-adenine-N1-oxide, and two isomers of dR-FAPy arising from radical attacks at C4 and C5, may be considered novel in the present study. Unlike radiation-derived [Formula: see text], the radical under study is difficult to eliminate due to its generation in the proximity of the substrate molecules. It is proposed that the iron binds to the phosphate group and generates the radical in its vicinity. Strand breaks in dA(pdA)(11) resulting from the Fenton reaction are of two types, spontaneous and alkali-labile. Duplex DNA is less sensitive to attack by this radical, as its various degradation products are a subset of those obtained with monomer substrates and only dR-FAPy production is relatively enhanced for poly (dA): oligo (dT) as compared to those from other substrates.
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26
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Verdan AM, Wang HC, García CR, Henry WP, Brumaghim JL. Iron binding of 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin: Implications for the antioxidant activity of flavonols with competing metal binding sites. J Inorg Biochem 2011; 105:1314-22. [DOI: 10.1016/j.jinorgbio.2011.07.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Revised: 07/19/2011] [Accepted: 07/20/2011] [Indexed: 10/17/2022]
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27
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Battin EE, Zimmerman MT, Ramoutar RR, Quarles CE, Brumaghim JL. Preventing metal-mediated oxidative DNA damage with selenium compounds. Metallomics 2011; 3:503-12. [DOI: 10.1039/c0mt00063a] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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28
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Sang Y, Zhang L, Li YF, Chen LQ, Xu JL, Huang CZ. A visual detection of hydrogen peroxide on the basis of Fenton reaction with gold nanoparticles. Anal Chim Acta 2010; 659:224-8. [DOI: 10.1016/j.aca.2009.11.031] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2009] [Revised: 11/12/2009] [Accepted: 11/13/2009] [Indexed: 10/20/2022]
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29
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Perron NR, Wang HC, DeGuire SN, Jenkins M, Lawson M, Brumaghim JL. Kinetics of iron oxidation upon polyphenol binding. Dalton Trans 2010; 39:9982-7. [DOI: 10.1039/c0dt00752h] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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30
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Abstract
With the aging of the population, we are seeing a global increase in the prevalence of age-related disorders, especially in developed countries. Chronic diseases disproportionately affect the older segment of the population, contributing to disability, a diminished quality of life and an increase in healthcare costs. Increased life expectancy reflects the success of contemporary medicine, which must now respond to the challenges created by this achievement, including the growing burden of chronic illnesses, injuries and disabilities. A well-developed theoretical framework is required to understand the molecular basis of aging. Such a framework is a prerequisite for the development of clinical interventions that will constitute an efficient response to the challenge of age-related health issues. This review critically analyzes the experimental evidence that supports and refutes the Free Radical/Mitochondrial Theory of Aging, which has dominated the field of aging research for almost half a century.
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Affiliation(s)
- Mikhail F Alexeyev
- Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, AL 36688, USA.
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31
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Shokolenko I, Venediktova N, Bochkareva A, Wilson GL, Alexeyev MF. Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Res 2009; 37:2539-48. [PMID: 19264794 PMCID: PMC2677867 DOI: 10.1093/nar/gkp100] [Citation(s) in RCA: 386] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mitochondrial DNA (mtDNA) is located in close proximity of the respiratory chains, which are the main cellular source of reactive oxygen species (ROS). ROS can induce oxidative base lesions in mtDNA and are believed to be an important cause of the mtDNA mutations, which accumulate with aging and in diseased states. However, recent studies indicate that cumulative levels of base substitutions in mtDNA can be very low even in old individuals. Considering the reduced complement of DNA repair pathways available in mitochondria and higher susceptibility of mtDNA to oxidative damage than nDNA, it is presently unclear how mitochondria manage to maintain the integrity of their genetic information in the face of the permanent exposure to ROS. Here we show that oxidative stress can lead to the degradation of mtDNA and that strand breaks and abasic sites prevail over mutagenic base lesions in ROS-damaged mtDNA. Furthermore, we found that inhibition of base excision repair enhanced mtDNA degradation in response to both oxidative and alkylating damage. These observations suggest a novel mechanism for the protection of mtDNA against oxidative insults whereby a higher incidence of lesions to the sugar–phosphate backbone induces degradation of damaged mtDNA and prevents the accumulation of mutagenic base lesions.
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Affiliation(s)
- Inna Shokolenko
- Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, AL 36688, USA
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32
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Molina MDC, Anchordoquy TJ. Formulation strategies to minimize oxidative damage in lyophilized lipid/DNA complexes during storage. J Pharm Sci 2009; 97:5089-105. [PMID: 18399563 DOI: 10.1002/jps.21365] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
It has been shown that degradation of lipid/DNA complexes (lipoplexes) continues in the dried state during storage. The goal of this study was to evaluate the ability of various strategies to minimize the formation of reactive oxygen species (ROS) in lyophilized lipoplexes during storage, including metal removal from reagents, air displacement, and fortification with chelator/antioxidant agents. Formulations containing individual chelator (DTPA) and antioxidants (L-methionine or alpha-tocopherol), or in combination, were subjected to lyophilization. Accelerated storage conditions were investigated and physico-chemical characteristics and biological activity of samples were monitored at different time intervals. Generation of ROS during storage was determined by adding proxyl fluorescamine to the formulations prior to freeze-drying. Lipid peroxidation was assessed by monitoring the formation of thiobarbituric reactive substances (TBARS) and lipid hydroperoxides. We also assessed the effect of increased moisture content on the chemical and biological stability of lipoplexes containing additives. Our results show that both ROS and TBARS are generated in lyophilized cakes during storage, and that agents such as DTPA or alpha-tocopherol are efficient in protecting lipid/DNA complexes against oxidative damage in the dried state. Our experiments also indicate that higher residual moisture has a deleterious effect on the stability of lipid/DNA complexes during storage.
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33
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Battin EE, Brumaghim JL. Metal specificity in DNA damage prevention by sulfur antioxidants. J Inorg Biochem 2008; 102:2036-42. [DOI: 10.1016/j.jinorgbio.2008.06.010] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2008] [Revised: 06/04/2008] [Accepted: 06/14/2008] [Indexed: 01/30/2023]
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34
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Degradation of lyophilized lipid/DNA complexes during storage: The role of lipid and reactive oxygen species. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2008; 1778:2119-26. [DOI: 10.1016/j.bbamem.2008.04.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2007] [Revised: 04/03/2008] [Accepted: 04/03/2008] [Indexed: 11/18/2022]
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35
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Perron NR, Hodges JN, Jenkins M, Brumaghim JL. Predicting How Polyphenol Antioxidants Prevent DNA Damage by Binding to Iron. Inorg Chem 2008; 47:6153-61. [DOI: 10.1021/ic7022727] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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36
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Nicolaescu AR, Wiest O, Kamat PV. Mechanistic pathways of the hydroxyl radical reactions of quinoline. 1. Identification, distribution, and yields of hydroxylated products. J Phys Chem A 2007; 109:2822-8. [PMID: 16833596 DOI: 10.1021/jp0450179] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The mechanistic details of the hydroxyl radical-induced transformations of quinoline have been elucidated. The nature and distribution of the final products have provided insight into the preferential attack of the hydroxyl radicals at different sites on the aromatic rings. Hydroxylated products at all of the carbon atoms but one, C2, have been observed and quantified following controlled radiolysis of N2O-purged aqueous quinoline solutions. The difference in the growth pattern and the lifetime of the monohydroxylated products under radiolytic conditions, as well as the formation of high-molecular-weight products (e.g., quinoline dimers), shows the complexity of the OH reaction pathways. The radiolytic yields (G values) for the degradation of the quinoline and the formation of the hydroxylated products are calculated in the absence and in the presence of an oxidant, K3Fe(CN)6. The addition of K3Fe(CN)6 changes only the distribution of the hydroxylated products. These experiments indicate that the nature of the hydroxylated products is determined in the initial addition step of the reaction of the hydroxyl radical with quinoline, whereas the chemistry of the OH adducts is relevant to the distribution of the final products. The discrepancy between the products of -radiolysis and the photo-Fenton reaction of quinoline is also discussed.
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Affiliation(s)
- A Roxana Nicolaescu
- Radiation Laboratory, University of Notre Dame, Notre Dame, Indiana 46556-0579, USA.
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37
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Ramoutar RR, Brumaghim JL. Effects of inorganic selenium compounds on oxidative DNA damage. J Inorg Biochem 2007; 101:1028-35. [PMID: 17531322 DOI: 10.1016/j.jinorgbio.2007.03.016] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2006] [Revised: 03/29/2007] [Accepted: 03/30/2007] [Indexed: 11/26/2022]
Abstract
Exposure of Escherichia coli or mammalian cells to H2O2 results in cell death due to iron-mediated DNA damage. Since selenium compounds have been examined for their ability to act as antioxidants to neutralize radical species, and inorganic selenium compounds are used to supplement protein mixes, infant formula, and animal feed, determining the effect of these compounds on DNA damage under conditions of oxidative stress is crucial. In the presence of Fe(II) and H2O2, the effects of Na2SeO4, Na2SeO3, SeO2 (0.5-5000 microM), and Na2Se (0.5-200 microM) on DNA damage were quantified using gel electrophoresis. Both Na2SeO4 and Na2Se have no effect on DNA damage, whereas SeO2 inhibits DNA damage and Na2SeO3 shows antioxidant or pro-oxidant activity depending on H2O2 concentration. Similar electrophoresis experiments with [Fe(EDTA)](2-) (400 microM) and Na2SeO3 or SeO2 show that metal coordination by the selenium compound is required for antioxidant activity. In light of these results, Na2SeO4 may be safer than Na2SeO3 for nutritional supplements.
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Affiliation(s)
- Ria R Ramoutar
- Department of Chemistry, Clemson University, Clemson, SC 29634, USA
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Molina MDC, Anchordoquy TJ. Metal contaminants promote degradation of lipid/DNA complexes during lyophilization. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2006; 1768:669-77. [PMID: 17224131 PMCID: PMC1851895 DOI: 10.1016/j.bbamem.2006.12.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Revised: 11/30/2006] [Accepted: 12/05/2006] [Indexed: 10/23/2022]
Abstract
Oxidation reactions represent an important degradation pathway of nucleic acid-based pharmaceuticals. To evaluate the role of metal contamination and chelating agents in the formation of reactive oxygen species (ROS) during lyophilization, ROS generation and the stability of lipid/DNA complexes were investigated. Trehalose-containing formulations were lyophilized with different levels of transition metals. ROS generation was examined by adding proxyl fluorescamine to the formulations prior to freeze-drying. Results show that ROS were generated during lyophilization, and both supercoil content and transfection rates decreased as the levels of metal-induced ROS increased. The experiments incorporating chelators demonstrated that some of these agents (e.g., DTPA, desferal) clearly suppress ROS generation, while others (e.g., EDTA) enhance ROS. Surprisingly, there was not a strong correlation of ROS generated in the presence of chelators with the maintenance of supercoil content. In this study, we demonstrated the adverse effects of the presence of metals (especially Fe(2+)) in nonviral vector formulations. While some chelators attenuate ROS generation and preserve DNA integrity, the effects of these additives on vector stability during lyophilization are difficult to predict. Further study is needed to develop potent formulation strategies that inhibit ROS generation and DNA degradation during lyophilization and storage.
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Affiliation(s)
- Marion d C Molina
- Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center School of Pharmacy, C238, Denver, CO 80262, USA.
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Boucher D, Testard I, Averbeck D. Low levels of clustered oxidative DNA damage induced at low and high LET irradiation in mammalian cells. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2006; 45:267-76. [PMID: 17047977 DOI: 10.1007/s00411-006-0070-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2006] [Accepted: 09/18/2006] [Indexed: 05/12/2023]
Abstract
DNA double-strand breaks (DSBs) and locally multiply damaged sites (LMDS) induced by ionizing radiation (IR) are considered to be very genotoxic in mammalian cells. LMDS consist of two or more clustered DNA lesions including oxidative damage locally formed within one or two helical turns by single radiation tracks following local energy deposition. They are thought to be frequently induced by IR but not by normal oxidative metabolism. In mammalian cells, LMDS are detected after specific enzymatic treatments transforming these lesions into additional DSBs that can be revealed by pulsed-field gel electrophoresis (PFGE). Here, we studied radiation-induced DSBs and LMDS in Chinese hamster ovary cells (CHO-K1). After addition of the iron chelator deferoxamine (DFO) or the antioxidant glutathione (GSH) to the cell lysis solution, we observed reduced spontaneous DNA fragmentation and a clear dose-dependent increase of radiation-induced DSBs. LMDS induction, however, was close to background levels, independently of dose, dose rate, temperature and radiation quality (low and high LET). Under these experimental conditions, artefactual oxidative DNA damage during cell lysis could not anymore be confounded with LMDS. We thus show that radiation-induced LMDS composed of oxidized purines or pyrimidines are much less frequent than hitherto reported, and suggest that they may be of minor importance in the radiation response than DSBs. We speculate that complex DSBs with oxidized ends may constitute the main part of radiation-induced clustered lesions. However, this needs further studies.
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Affiliation(s)
- Didier Boucher
- Institut Curie-Section Recherche, UMR 2027 CNRS/I.C., LCR V28 CEA, Bâtiment 110, Centre Universitaire, 91405, Orsay Cedex, France
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Mugweru A, Wang B, Rusling J. Voltammetric sensor for oxidized DNA using ultrathin films of osmium and ruthenium metallopolymers. Anal Chem 2006; 76:5557-63. [PMID: 15362921 DOI: 10.1021/ac049375j] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Films containing [Os(bpy)2(PVP)10Cl]+ and [Ru(bpy)2(PVP)10Cl]+ metallopolymers were assembled layer by layer on pyrolytic graphite electrodes to make sensors that selectively detect oxidized DNA. These films showed reversible, independent electrochemistry for electroactive Os3+/Os2+ and Ru3+/Ru2+ centers, with formal potentials of 0.34 and 0.76 V vs SCE, respectively. The combination of ruthenium and osmium metallopolymers in the films provided a catalytic Os square wave voltammetry (SWV) peak that is mainly selective for 8-oxoguanine and the detection of other oxidized nucleobases from the Ru peak. The method is applicable to measurements on DNA in solution or DNA incorporated into films. Using the Os SWV peak, 1 oxidized nucleobase in 6000 was detected. The sensor is simple and inexpensive, and the approach may be useful for the detection of oxidized DNA as a clinical biomarker for oxidative stress.
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Affiliation(s)
- Amos Mugweru
- Department of Chemistry, University of Connecticut, U-60, 55 North Eagleville Road, Storrs, Connecticut 06269-3060, USA
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41
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Zeller T, Moskvin OV, Li K, Klug G, Gomelsky M. Transcriptome and physiological responses to hydrogen peroxide of the facultatively phototrophic bacterium Rhodobacter sphaeroides. J Bacteriol 2005; 187:7232-42. [PMID: 16237007 PMCID: PMC1272974 DOI: 10.1128/jb.187.21.7232-7242.2005] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The transcriptome responses to hydrogen peroxide, H2O2, of the facultatively phototrophic bacterium Rhodobacter sphaeroides grown under semiaerobic conditions were investigated. At 7 min after the addition of 1 mM H2O2, the expression of approximately 9% of all genes (total, 394) was changed reliably by at least twofold. At 30 min, the number of genes (total, 88) and the magnitude of expression changes were much lower, indicating rapid recovery from stress. Two types of responses were observed: (i) an H2O2 stress response per se and (ii) a shift to high-oxygen metabolism. The former response involved the upregulation of genes for H2O2 detoxification, protein folding and proteolysis, DNA damage repair, iron transport and storage, iron-sulfur cluster repair, and the downregulation of genes for protein translation, motility, and cell wall and lipopolysaccharide synthesis. The shift to high-oxygen metabolism was evident from the differential regulation of genes for aerobic electron transport chain components and the downregulation of tetrapyrrole biosynthesis and photosystem genes. The abundance of photosynthetic complexes was decreased upon prolonged exposure of R. sphaeroides to H2O2, thus confirming the physiological significance of the transcriptome data. The regulatory pathways mediating the shift to high-oxygen metabolism were investigated. They involved the anaerobic activator FnrL and the antirepressor-repressor AppA-PpsR system. The transcription of FnrL-dependent genes was down at 7 min, apparently due to the transient inactivation by H2O2 of the iron-sulfur cluster of FnrL. The transcription of the AppA-PpsR-dependent genes was down at 30 min, apparently due to the significant decrease in appA mRNA.
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Affiliation(s)
- Tanja Zeller
- Institut für Mikrobiologie und Molekularbiologie, University of Giessen, Germany
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Ouameur AA, Arakawa H, Ahmad R, Naoui M, Tajmir-Riahi HA. A Comparative study of Fe(II) and Fe(III) interactions with DNA duplex: major and minor grooves bindings. DNA Cell Biol 2005; 24:394-401. [PMID: 15941392 DOI: 10.1089/dna.2005.24.394] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The involvement of the Fe cations in autoxidation in cells and tissues is well documented. DNA is a major target in such reaction, and can chelate Fe cation in many ways. The present study was designed to examine the interaction of calf-thymus DNA with Fe(II) and Fe(III), in aqueous solution at pH 6.5 with cation/DNA (P) (P = phosphate) molar ratios (r) of 1:160 to 1:2. Capillary electrophoresis and Fourier transform infrared (FTIR) difference spectroscopic methods were used to determine the cation binding site, the binding constant, helix stability and DNA conformation in Fe-DNA complexes. Structural analysis showed that at low cation concentration (r = 1/80 and 1/40), Fe(II) binds DNA through guanine N-7 and the backbone PO(2) group with specific binding constants of K(G) = 5.40 x 10(4) M(1) and K(P) = 2.40 x 10(4) M(1). At higher cation content, Fe(II) bindings to adenine N-7 and thymine O-2 are included. The Fe(III) cation shows stronger interaction with DNA bases and the backbone phosphate group. At low cation concentration (r = 1:80), Fe(III) binds mainly to the backbone phosphate group, while at higher metal ion content, cation binding to both guanine N-7 atom and the backbone phosphate group is prevailing with specific binding constants of K(G) = 1.36 x 10(5) M(-1) and K(P) = 5.50 x 10(4) M(-1). At r = 1:10, Fe(II) binding causes a minor helix destabilization, whereas Fe(III) induces DNA condensation. No major DNA conformational changes occurred upon iron complexation and DNA remains in the B-family structure.
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Affiliation(s)
- A Ahmed Ouameur
- Department of Chemistry-Biology, University of Québec at Trois-Rivières, Quebec, Canada
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Fujimoto Y, Ohtsuka S, Miyashita H, Sakuma S. Effect of Tetrahydrobiopterin on Copper-Mediated DNA Oxidation: Its Prooxidant Property. J Clin Biochem Nutr 2005. [DOI: 10.3164/jcbn.36.51] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Dennany L, Forster RJ, White B, Smyth M, Rusling JF. Direct electrochemiluminescence detection of oxidized DNA in ultrathin films containing [Os(bpy)2(PVP)10]2+. J Am Chem Soc 2004; 126:8835-41. [PMID: 15250737 DOI: 10.1021/ja048615+] [Citation(s) in RCA: 116] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Direct electrochemiluminescence (ECL) involving oxidized DNA was demonstrated in ultrathin films of cationic polymer [Os(bpy)2(PVP)10]2+ [PVP = poly(vinyl pyridine)] assembled layer-by-layer with DNA or oligonucleotides. Electrochemically oxidized Os(II) sites generated ECL from films containing oxo-guanines on DNA formed by chemical oxidation using Fenton reagent. Films combining DNA, [Ru(bpy)2(PVP)10]2+, and [Os(bpy)2(PVP)10]2+ had Os(II) sites that produced ECL specific for oxidized DNA, and Ru(II) sites gave ECL from reaction with oxo-adenines, chemically damaged DNA, and possibly from cleaved DNA strands.
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Affiliation(s)
- Lynn Dennany
- National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland
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Matsufuji H, Shibamoto T. The role of EDTA in malonaldehyde formation from DNA oxidized by Fenton reagent systems. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2004; 52:3136-3140. [PMID: 15137865 DOI: 10.1021/jf035337+] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Calf thymus DNA was oxidized by various Fenton reagent systems [Fe(II)/H(2)O(2)] with or without ethylenediamine tetraacetic acid (EDTA) under different reaction conditions. Calf DNA was also oxidized by a modified Fenton reagent (Fe(III)/H(2)O(2)/ascorbic acid) with EDTA. Malonaldehyde (MA) formed from DNA was derivatized into 1-methyl hydrazine, which was subsequently analyzed by gas chromatography with a nitrogen-phosphorus detector. MA formation increased linearly with an increase of Fe(II) concentration. MA formation reached a plateau at nearly 2 mmol/L of Fe(II) with 0.5 mmol/L of H(2)O(2). Addition of EDTA increased MA formation from DNA nearly 5 times. When DNA was oxidized with various amount of ethanol, MA formation decreased with an increase of ethanol concentration, either with or without EDTA. The rate of inhibition was greater without EDTA than with EDTA. When DNA was oxidized by a modified Fenton reagent, MA formation linearly increased with the increase of DNA. Ascorbic acid alone produced some MA upon oxidation.
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Affiliation(s)
- Hiroshi Matsufuji
- Department of Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, California 95616, USA
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Kosinska W, Pelle E, von Pressentin MDM, Chen M, Guttenplan JB. Comparative mutagenicities of bleomycin and ferric-nitrilotriacetate in lacZ mice. Cancer Lett 2002; 187:41-6. [PMID: 12359349 DOI: 10.1016/s0304-3835(02)00382-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Bleomycin and ferric nitrilotriacetate (Fe-NTA) give rise to reactive oxygen species (ROS). Bleomycin was mutagenic in lacZ mouse kidney, liver and lung, but Fe-NTA was non-mutagenic in kidney and lung and marginally mutagenic in liver. Fe-NTA-treatment led to an increase in 8-hydroxydeoxyguanosine levels in kidney and liver, while the corresponding levels in bleomycin-treated mice were if anything, lower than those for bleomycin. It appears that factors other than simply the ability to generate ROS, play a role in mutagenesis by these compounds.
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Affiliation(s)
- Wieslawa Kosinska
- Department of Basic Sciences, New York University, Dental Center, 345 East 24th Street, New York, NY 10100, USA
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Svoboda P, Harms-Ringdahl M. Kinetics of phosphate-mediated oxidation of ferrous iron and formation of 8-oxo-2'-deoxyguanosine in solutions of free 2'-deoxyguanosine and calf thymus DNA. BIOCHIMICA ET BIOPHYSICA ACTA 2002; 1571:45-54. [PMID: 12031289 DOI: 10.1016/s0304-4165(02)00205-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in solutions of free 2'-deoxyguanosine (dG) and calf thymus DNA (DNA) was compared for the diffusion-dependent and localised production of oxygen radicals from phosphate-mediated oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+). The oxidation of Fe2+ to Fe3+ was followed at 304 nm at pH 7.2 under aerobic conditions. Given that the concentration of Fe2+ >or=phosphate concentration, the rate of Fe2+ oxidation was significantly higher in DNA-phosphate as compared for the same concentration of inorganic phosphate. Phosphate catalysed oxidation of ferrous ions in solutions of dG or DNA led through the production of reactive oxygen species to the formation of 8-oxo-dG. The yield of 8-oxo-dG in solutions of dG or DNA correlated positively with the inorganic-/DNA-phosphate concentrations as well as with the concentrations of ferrous ions added. The yield of 8-oxo-dG per unit oxidised Fe2+ were similar for dG and DNA; thus, it differed markedly from radiation-induced 8-oxo-dG, where the yield in DNA was several fold higher. For DNA in solution, the localisation of the phosphate ferrous iron complex relative to the target is an important factor for the yield of 8-oxo-dG. This was supported from the observation that the yield of 8-oxo-dG in solutions of dG was significantly increased over that in DNA only when Fe2+ was oxidised in a high excess of inorganic phosphate (50 mM) and from the lower protection of DNA damage by the radical scavenger (hydroxymethyl)aminomethane (Tris)-HCl.
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Affiliation(s)
- Peter Svoboda
- Department of Genetic and Cellular Toxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden
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Abstract
Acid phosphatases (APs) are a family of enzymes that are widespread in nature, and can be found in many animal and plant species. Mystery surrounds the precise functional role of these molecular facilitators, despite much research. Yet, paradoxically, human APs have had considerable impact as tools of clinical investigation and intervention. One particular example is tartrate resistant acid phosphatase, which is detected in the serum in raised amounts accompanying pathological bone resorption. This article seeks to explore the identity and diversity of APs, and to demonstrate the relation between APs, human disease, and clinical diagnosis.
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Affiliation(s)
- H Bull
- Human and Clinical Research Group, School of Nursing, University of Nottingham, Derbyshire Royal Infirmary, Derby DE1 2QY, UK
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Theruvathu JA, Aravindakumar CT, Flyunt R, von Sonntag J, von Sonntag C. Fenton chemistry of 1,3-dimethyluracil. J Am Chem Soc 2001; 123:9007-14. [PMID: 11552808 DOI: 10.1021/ja0109794] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Hydroxyl radicals were generated in the Fenton reaction at pH 4 (Fe(2+) + H(2)O(2) --> Fe(3+) + .OH + OH-, k approximately equal to 60 L mol(-1) s(-1)) and by pulse radiolysis (for the determination of kinetic data). They react rapidly with 1,3-dimethyluracil, 1,3-DMU (k = 6 x 10(9) L mol(-1) s(-1)). With H(2)O(2) in excess and in the absence of O(2), 1,3-DMU consumption is 3.3 mol per mol Fe(2+). 1,3-DMUglycol is the major product (2.95 mol per mol Fe(2+)). Dimers, prominent products of .OH-induced reactions in the absence of Fe(2+)/Fe(3+) (Al-Sheikhly, M.; von Sonntag, C. Z. Naturforsch. 1983, 31b, 1622) are not formed. Addition of .OH to the C(5)-C(6) double bond of 1,3-DMU yields reducing C(6)-yl 1 and oxidizing C(5)-yl radicals 2 in a 4:1 ratio. The yield of reducing radicals was determined with tetranitromethane by following the buildup of nitroform anion. Reaction of 1 with Fe(3+) that builds up during the reaction or with H(2)O(2) gives rise to a short-chain reaction that is terminated by the reaction of Fe(2+) with 2, which re-forms 1,3-DMU. In the presence of O(2), 1.1 mol of 1,3-DMU and 0.6 mol of O(2) are consumed per mol Fe(2+) while 0.16 mol of 1,3-DMU-glycol and 0.17 mol of organic hydroperoxides (besides further unidentified products) are formed. In the presence of O(2), 1 and 2 are rapidly converted into the corresponding peroxyl radicals (k = 9.1 x 10(8) L mol(-1) s(-1)). Their bimolecular decay (2k = 1.1 x 10(9) L mol(-1) s(-1)) yields approximately 22% HO(2)./O(2).(-) in the course of fragmentation reactions involving the C(5)-C(6) bond. Reduction of Fe(3+) by O(2).(-) leads to an increase in .OH production that is partially offset by a consumption of Fe(2+) in its reaction with the peroxyl radicals (formation of organic hydroperoxides, k approximately 3 x 10(5) L mol(-1) s(-1); value derived by computer simulation).
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Affiliation(s)
- J A Theruvathu
- Max-Planck-Institut für Strahlenchemie, Stiftstrasse 34-36, P.O. Box 101365, D-45470-Mülheim an der Ruhr, Germany
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Djuric Z, Potter DW, Taffe BG, Strasburg GM. Comparison of iron-catalyzed DNA and lipid oxidation. J Biochem Mol Toxicol 2001; 15:114-9. [PMID: 11284053 DOI: 10.1002/jbt.7] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lipid and DNA oxidation catalyzed by iron(II) were compared in HEPES and phosphate buffers. Lipid peroxidation was examined in a sensitive liposome system constructed with a fluorescent probe that allowed us to examine the effects of both low and high iron concentrations. With liposomes made from synthetic 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine or from rat liver microsomal lipid, lipid peroxidation increased with iron concentration up to the range of 10--20 microM iron(II), but then rates decreased with further increases in iron concentration. This may be due to the limited amount of lipid peroxides available in liposomes for oxidation of iron(II) to generate equimolar iron(III), which is thought to be important for the initation of lipid peroxidation. Addition of hydrogen peroxide to incubations with 1--10 microM iron(II) decreased rates of lipid peroxidation, whereas addition of hydrogen peroxide to incubations with higher iron concentrations increased rates of lipid peroxidation. Thus, in this liposome system, sufficient peroxide from either within the lipid or from exogenous sources must be present to generate equimolar iron(II) and iron(III). With iron-catalyzed DNA oxidation, hydrogen peroxide always stimulated product formation. Phosphate buffer, which chelates iron but still allows for generation of hydroxyl radicals, inhibited lipid peroxidation but not DNA oxidation. HEPES buffer, which scavenges hydroxyl radicals, inhibited DNA oxidation, whereas lipid peroxidation was unaffected since presumably iron(II) and iron(III) were still available for reaction with liposomes in HEPES buffer.
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Affiliation(s)
- Z Djuric
- Barbara Ann Karmanos Cancer Institute, 110 East Warren, Detroit, MI, USA.
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