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Dufault RJ, Crider RA, Deth RC, Schnoll R, Gilbert SG, Lukiw WJ, Hitt AL. Higher rates of autism and attention deficit/hyperactivity disorder in American children: Are food quality issues impacting epigenetic inheritance? World J Clin Pediatr 2023; 12:25-37. [PMID: 37034430 PMCID: PMC10075020 DOI: 10.5409/wjcp.v12.i2.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/25/2022] [Accepted: 01/09/2023] [Indexed: 03/06/2023] Open
Abstract
In the United States, schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals. Pediatricians may play a key role in helping children access special education services. The number of children ages 6-21 in the United States receiving special education services increased 10.4% from 2006 to 2021. Children receiving special education services under the autism category increased 242% during the same period. The demand for special education services for children under the developmental delay and other health impaired categories increased by 184% and 83% respectively. Although student enrollment in American schools has remained stable since 2006, the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021. Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes. Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics. Dietary heavy metal exposures, especially inorganic mercury and lead may impact gene behavior across generations. In 2021, the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action. Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.
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Affiliation(s)
- Renee J Dufault
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- College of Graduate Health Studies, A.T. Still University, Kirksville, MO 63501, United States
| | - Raquel A Crider
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
| | - Richard C Deth
- Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33314, United States
| | - Roseanne Schnoll
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Department of Health and Nutrition Sciences, Brooklyn College of CUNY, Brooklyn, NY 11210, United States
| | - Steven G Gilbert
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Department of Research, Institute of Neurotoxicology and Neurological Disorders, Seattle, WA 98105, United States
| | - Walter J Lukiw
- LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States
| | - Amanda L Hitt
- Food Integrity Campaign, Government Accountability Project, Columbia, WA 20006, United States
- Department of Legal, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
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Li YQ, Wang Q, Liu R, Li GA, He JL, Huang F, Zhou YF. Associations of exposure to multiple metals with the risk of age-related cataract in Anhui, China: a case-control study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:4680-4693. [PMID: 35972654 DOI: 10.1007/s11356-022-22494-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 08/08/2022] [Indexed: 06/15/2023]
Abstract
It's well-known that multiple metal elements can lead to the change of oxidative stress response levels in vivo. However, their relationship with age-related cataract (ARC) had not been well studied. We designed a case-control study including 210 individuals with ARC and 210 matched control group. The metal levels in their urine specimens were measured using graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select representative metals into the multi-element model and reduce dimension. Multivariate logic analysis and Bayesian kernel machine regression (BKMR) were subsequently used to explore the association of ARC risk with multiple metal elements. We found that magnesium (Mg), chromium (Cr), arsenic (As), manganese (Mn), and selenium (Se) were positively associated with ARC in the single-element model. The multiple exposure model indicated a positive association between Mg and As, in which the OR in their highest quartile were 3.32 (95% CI: 1.24-8.89) and 7.09 (95% CI: 2.56-19.63). The BKMR model also showed the effect of As increased monotonically with its increasing concentration, and high levels of Mg and As had a significant positive effect on ARC risk. In conclusion, we found that exposure to multiple metals was associated with increased ARC risk. Further research is needed to verify these findings in the future.
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Affiliation(s)
- Yan-Qing Li
- Department of Ophthalmology, First Affiliated Hospital of Anhui Medical University, No.218, Jixi Road, Shushan District, Hefei, 230022, Anhui, China
| | - Qian Wang
- Department of Ophthalmology, First Affiliated Hospital of Anhui Medical University, No.218, Jixi Road, Shushan District, Hefei, 230022, Anhui, China
| | - Ran Liu
- Department of Ophthalmology, First Affiliated Hospital of Anhui Medical University, No.218, Jixi Road, Shushan District, Hefei, 230022, Anhui, China
| | - Guo-Ao Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Jia-Liu He
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Fen Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Yan-Feng Zhou
- Department of Ophthalmology, First Affiliated Hospital of Anhui Medical University, No.218, Jixi Road, Shushan District, Hefei, 230022, Anhui, China.
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Aziz J, Vaithilingam RD, Radzi Z, Rahman MT. Inflammatory Responses in Periodontitis with or Without Rheumatoid Arthritis Alter Salivary Metallothionein and Zinc. Biol Trace Elem Res 2022; 201:3162-3174. [PMID: 36094693 DOI: 10.1007/s12011-022-03416-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 09/06/2022] [Indexed: 11/26/2022]
Abstract
Periodontitis (PD) and rheumatoid arthritis (RA) are causally linked by their common inflammatory responses, yet it is largely unknown if these inflammatory responses might have an impact on salivary metallothionein (MT), zinc (Zn), and calcium (Ca) content. In this study, we analysed salivary concentrations of pro-inflammatory (IFN-γ, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines, as well as MT, Zn, and Ca in four groups of participants, namely control (without PD or RA, n = 21), PD (n = 21), RA (n = 21), or RAPD (n = 19). As expected, an increased amount of salivary pro-inflammatory cytokines were observed in the PD, RA, and RAPD groups. While Ca concentration was not significantly different between the groups, Zn concentration was lower in the PD, RA, and RAPD groups compared to the control group (p < 0.05). These groups also expressed higher MT/Zn ratios compared to the control group (p < 0.05). Unlike the control group, concentrations of inflammatory cytokines, MT, Zn, and Ca correlated with each other in the PD, RA, and RAPD groups (p < 0.05). Additionally, comorbidity of PD and RA appears to have a cumulative immuno-pathological impact that warrants further investigation. This study suggests that, in addition to inflammatory cytokines, salivary MT and Zn could reflect the severity of PD with or without RA, hence providing an important biomarker for diagnosis.
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Affiliation(s)
- Jazli Aziz
- Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
- Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Rathna Devi Vaithilingam
- Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Zamri Radzi
- Department of Paediatric Dentistry & Orthodontics, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
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De Francisco P, Martín-González A, Rodriguez-Martín D, Díaz S. Interactions with Arsenic: Mechanisms of Toxicity and Cellular Resistance in Eukaryotic Microorganisms. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:12226. [PMID: 34831982 PMCID: PMC8618186 DOI: 10.3390/ijerph182212226] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 12/27/2022]
Abstract
Arsenic (As) is quite an abundant metalloid, with ancient origin and ubiquitous distribution, which represents a severe environmental risk and a global problem for public health. Microbial exposure to As compounds in the environment has happened since the beginning of time. Selective pressure has induced the evolution of various genetic systems conferring useful capacities in many microorganisms to detoxify and even use arsenic, as an energy source. This review summarizes the microbial impact of the As biogeochemical cycle. Moreover, the poorly known adverse effects of this element on eukaryotic microbes, as well as the As uptake and detoxification mechanisms developed by yeast and protists, are discussed. Finally, an outlook of As microbial remediation makes evident the knowledge gaps and the necessity of new approaches to mitigate this environmental challenge.
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Affiliation(s)
| | - Ana Martín-González
- Department of Genetics, Physiology and Microbiology, Faculty of Biology, C/José Antonio Novais, 12, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain;
| | - Daniel Rodriguez-Martín
- Animal Health Research Centre (CISA), National Institute for Agricultural and Food Research and Technology (INIA-CSIC), 28130 Madrid, Spain;
| | - Silvia Díaz
- Department of Genetics, Physiology and Microbiology, Faculty of Biology, C/José Antonio Novais, 12, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain;
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Experimental acute arsenic toxicity in Balb/c mice: organic markers and splenic involvement. ACTA ACUST UNITED AC 2021; 41:99-110. [PMID: 33761193 PMCID: PMC8055596 DOI: 10.7705/biomedica.5485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Indexed: 11/21/2022]
Abstract
Introduction: Arsenic is an environmental toxic present worldwide. In men and animals, various organs and tissues are targets of its deleterious effects including those of the immune system.
Objective: To determine acute arsenic toxicity in tissues and target cells of Balb/c mice using an in vivo methodology.
Materials and methods: We injected Balb/c mice intraperitoneally with 9.5 or 19 mg/kg of sodium arsenite (NaAsO2), or an equivalent volume of physiological solution as a control (with 3 per experimental group). After 30 minutes, the animals were sacrificed to obtain spleen, thymus, liver, kidneys, and blood. We determined arsenic, polyphenols, and iron concentrations in each sample and we evaluated the oxidative markers (peroxides, advanced products of protein oxidation, and free sulfhydryl groups). In splenocytes from the spleen, cell viability and mitochondrial potential were also determined.
Results: The exposure to an acute dose of NaAsO2 reduced the mitochondrial function of splenocytes, which resulted in cell death. Simultaneously, the confirmed presence of arsenic in spleen samples and the resulting cytotoxicity occurred with a decrease in polyphenols, free sulfhydryl groups, and an alteration in the content and distribution of iron, but did not increase the production of peroxides.
Conclusion: These findings provide scientific evidence about changes occurring in biomarkers involved in the immunotoxicity of arsenic and offer a methodology for testing possible treatments against the deleterious action of this compound on the immune system.
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Fu J, Zhong C, Zhang P, Gao Q, Zong G, Zhou Y, Cao G. A Novel Mobile Element ICE RspD18B in Rheinheimera sp. D18 Contributes to Antibiotic and Arsenic Resistance. Front Microbiol 2020; 11:616364. [PMID: 33391249 PMCID: PMC7775301 DOI: 10.3389/fmicb.2020.616364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 11/30/2020] [Indexed: 11/16/2022] Open
Abstract
Antibiotics and organoarsenical compounds are frequently used as feed additives in many countries. However, these compounds can cause serious antibiotic and arsenic (As) pollution in the environment, and the spread of antibiotic and As resistance genes from the environment. In this report, we characterized the 28.5 kb genomic island (GI), named as ICERspD18B, as a novel chromosomal integrative and conjugative element (ICE) in multidrug-resistant Rheinheimera sp. D18. Notably, ICERspD18B contains six antibiotic resistance genes (ARGs) and an arsenic tolerance operon, as well as genes encoding conjugative transfer proteins of a type IV secretion system, relaxase, site-specific integrase, and DNA replication or partitioning proteins. The transconjugant strain 25D18-B4 was generated using Escherichia coli 25DN as the recipient strain. ICERspD18B was inserted into 3'-end of the guaA gene in 25D18-B4. In addition, 25D18-B4 had markedly higher minimum inhibitory concentrations for arsenic compounds and antibiotics when compared to the parental E. coli strain. These findings demonstrated that the integrative and conjugative element ICERspD18B could mediate both antibiotic and arsenic resistance in Rheinheimera sp. D18 and the transconjugant 25D18-B4.
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Affiliation(s)
- Jiafang Fu
- Department of Epidemiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.,College of Biomedical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Chuanqing Zhong
- School of Municipal and Environmental Engineering, Shandong Jianzhu University, Jinan, China
| | - Peipei Zhang
- Department of Epidemiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.,College of Biomedical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.,Key Laboratory for Biotech-Drugs of National Health Commission, Department of Microbiology, Jinan, China
| | - Qingxia Gao
- College of Biomedical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Gongli Zong
- Department of Epidemiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.,College of Biomedical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.,Key Laboratory for Biotech-Drugs of National Health Commission, Department of Microbiology, Jinan, China
| | - Yingping Zhou
- School of Municipal and Environmental Engineering, Shandong Jianzhu University, Jinan, China
| | - Guangxiang Cao
- Department of Epidemiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.,College of Biomedical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.,Key Laboratory for Biotech-Drugs of National Health Commission, Department of Microbiology, Jinan, China
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7
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Toxicity, Physiological, and Ultrastructural Effects of Arsenic and Cadmium on the Extremophilic Microalga Chlamydomonas acidophila. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17051650. [PMID: 32138382 PMCID: PMC7084474 DOI: 10.3390/ijerph17051650] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/20/2020] [Accepted: 02/24/2020] [Indexed: 01/23/2023]
Abstract
The cytotoxicity of cadmium (Cd), arsenate (As(V)), and arsenite (As(III)) on a strain of Chlamydomonas acidophila, isolated from the Rio Tinto, an acidic environment containing high metal(l)oid concentrations, was analyzed. We used a broad array of methods to produce complementary information: cell viability and reactive oxygen species (ROS) generation measures, ultrastructural observations, transmission electron microscopy energy dispersive x-ray microanalysis (TEM-XEDS), and gene expression. This acidophilic microorganism was affected differently by the tested metal/metalloid: It showed high resistance to arsenic while Cd was the most toxic heavy metal, showing an LC50 = 1.94 µM. Arsenite was almost four-fold more toxic (LC50= 10.91 mM) than arsenate (LC50 = 41.63 mM). Assessment of ROS generation indicated that both arsenic oxidation states generate superoxide anions. Ultrastructural analysis of exposed cells revealed that stigma, chloroplast, nucleus, and mitochondria were the main toxicity targets. Intense vacuolization and accumulation of energy reserves (starch deposits and lipid droplets) were observed after treatments. Electron-dense intracellular nanoparticle-like formation appeared in two cellular locations: inside cytoplasmic vacuoles and entrapped into the capsule, around each cell. The chemical nature (Cd or As) of these intracellular deposits was confirmed by TEM-XEDS. Additionally, they also contained an unexpected high content in phosphorous, which might support an essential role of poly-phosphates in metal resistance.
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Wong CP, Dashner-Titus EJ, Alvarez SC, Chase TT, Hudson LG, Ho E. Zinc Deficiency and Arsenic Exposure Can Act Both Independently or Cooperatively to Affect Zinc Status, Oxidative Stress, and Inflammatory Response. Biol Trace Elem Res 2019; 191:370-381. [PMID: 30635848 PMCID: PMC6625954 DOI: 10.1007/s12011-019-1631-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 01/01/2019] [Indexed: 12/16/2022]
Abstract
The negative health impact of zinc deficiency overlaps significantly with arsenic exposure, and is associated with increased risk for chronic diseases. Arsenic contamination in the groundwater often co-exists in regions of the world that are prone to zinc deficiency. Notably, low zinc status shares many hallmarks of arsenic exposure, including increased oxidative stress and inflammation. Despite their common targets and frequent co-distribution in the population, little is known regarding the interaction between zinc deficiency and arsenic exposure. In this study, we tested the effect of arsenic exposure at environmentally relevant doses in combination with a physiologically relevant level of zinc deficiency (marginal zinc deficiency) on zinc status, oxidative damage, and inflammation. In cell culture, zinc-deficient THP-1 monocytes co-exposed with arsenic resulted in further reduction in intracellular zinc, as well as further increase in oxidative stress and inflammatory markers. In an animal study, zinc-deficient mice had further decrease in zinc status when co-exposed to arsenic. Zinc deficiency, but not arsenic exposure, resulted in an increase in baseline transcript abundance of inflammatory markers in the liver. Upon lipopolysaccharide challenge to elicit an acute inflammatory response, arsenic exposure, but not zinc deficiency, resulted in an increase in proinflammatory response. In summary, zinc deficiency and arsenic exposure can function independently or cooperatively to affect zinc status, oxidant stress, and proinflammatory response. The results highlight the need to consider both nutritional status and arsenic exposures together when considering their impact on health outcomes in susceptible populations.
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Affiliation(s)
- Carmen P Wong
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA
| | - Erica J Dashner-Titus
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA
| | - Sandra C Alvarez
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA
| | - Tyler T Chase
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA
| | - Laurie G Hudson
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA
| | - Emily Ho
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA.
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.
- Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health, Oregon State University, Corvallis, OR, 97331, USA.
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Tsui KH, Hou CP, Chang KS, Lin YH, Feng TH, Chen CC, Shin YS, Juang HH. Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells. Int J Mol Sci 2019; 20:ijms20040980. [PMID: 30813460 PMCID: PMC6413184 DOI: 10.3390/ijms20040980] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 02/19/2019] [Accepted: 02/20/2019] [Indexed: 12/18/2022] Open
Abstract
Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS₂O₃) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.
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Affiliation(s)
- Ke-Hung Tsui
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Chen-Pang Hou
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan.
- Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Kang-Shuo Chang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Yu-Hsiang Lin
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan.
- Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Tsui-Hsia Feng
- School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Chiu-Chun Chen
- Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Yi-Syuan Shin
- Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
| | - Horng-Heng Juang
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan.
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
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Rahman MT, Karim MM. Metallothionein: a Potential Link in the Regulation of Zinc in Nutritional Immunity. Biol Trace Elem Res 2018; 182:1-13. [PMID: 28585004 DOI: 10.1007/s12011-017-1061-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/22/2017] [Indexed: 01/03/2023]
Abstract
Nutritional immunity describes mechanisms for withholding essential transition metals as well as directing the toxicity of these metals against infectious agents. Zinc is one of these transition elements that are essential for both humans and microbial pathogens. At the same time, Zn can be toxic both for man and microbes if its concentration is higher than the tolerance limit. Therefore a "delicate" balance of Zn must be maintained to keep the immune cells surveilling while making the level of Zn either to starve or to intoxicate the pathogens. On the other hand, the invading pathogens will exploit the host Zn pool for its survival and replication. Apparently, different sets of protein in human and bacteria are involved to maintain their Zn need. Metallothionein (MT)-a group of low molecular weight proteins, is well known for its Zn-binding ability and is expected to play an important role in that Zn balance at the time of active infection. However, the differences in structural, functional, and molecular control of biosynthesis between human and bacterial MT might play an important role to determine the proper use of Zn and the winning side. The current review explains the possible involvement of human and bacterial MT at the time of infection to control and exploit Zn for their need.
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11
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Irvine GW, Stillman MJ. Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins. Int J Mol Sci 2017; 18:ijms18050913. [PMID: 28445428 PMCID: PMC5454826 DOI: 10.3390/ijms18050913] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 04/18/2017] [Accepted: 04/20/2017] [Indexed: 12/23/2022] Open
Abstract
Structural information regarding metallothioneins (MTs) has been hard to come by due to its highly dynamic nature in the absence of metal-thiolate cluster formation and crystallization difficulties. Thus, typical spectroscopic methods for structural determination are limited in their usefulness when applied to MTs. Mass spectrometric methods have revolutionized our understanding of protein dynamics, structure, and folding. Recently, advances have been made in residue modification mass spectrometry in order to probe the hard-to-characterize structure of apo- and partially metalated MTs. By using different cysteine specific alkylation reagents, time dependent electrospray ionization mass spectrometry (ESI-MS), and step-wise “snapshot” ESI-MS, we are beginning to understand the dynamics of the conformers of apo-MT and related species. In this review we highlight recent papers that use these and similar techniques for structure elucidation and attempt to explain in a concise manner the data interpretations of these complex methods. We expect increasing resolution in our picture of the structural conformations of metal-free MTs as these techniques are more widely adopted and combined with other promising tools for structural elucidation.
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Affiliation(s)
- Gordon W Irvine
- Department of Chemistry, The University of Western Ontario, London, ON N6A 3K7, Canada.
| | - Martin J Stillman
- Department of Chemistry, The University of Western Ontario, London, ON N6A 3K7, Canada.
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12
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Rahman MT, Haque N, Abu Kasim NH, De Ley M. Origin, Function, and Fate of Metallothionein in Human Blood. Rev Physiol Biochem Pharmacol 2017; 173:41-62. [PMID: 28417197 DOI: 10.1007/112_2017_1] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS), infections, and temperature are well-known metallothionein (MT) inducers in human blood. The current review aims to summarize synthesis, function, and fate of human blood MT in response to the known MT inducers. Part of the MTs that are synthesized in different organs such as the liver, kidney, and spleen is transported and stored in different blood cells and in plasma. Cells of the circulatory system also synthesize MT. From the circulation, MT returns to the kidney where the metal-bound MTs are degraded to release the metal ion that in turn induces MT expression therein. The blood MTs play important roles in metal detoxification, transportation, and storage. By neutralizing ROS, MTs protect blood cells from oxidative stress-induced cytotoxicity and genotoxicity. Arguably, MTs are also involved in immune suppression. Given the permeating distribution of blood MT throughout the body as well as its diverse role in the protection against harmful environmental factors and in metal homeostasis, MT could be better recognized as a major public health protein.
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Affiliation(s)
| | - Nazmul Haque
- Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
- Regenerative Dentistry Research Group, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Noor Hayaty Abu Kasim
- Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
- Regenerative Dentistry Research Group, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Marc De Ley
- Laboratorium voor Biochemie, KU Leuven, Celestijnenlaan 200G, Postbus 2413, Heverlee, 3001, Leuven, Belgium
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Metallothionein does not sequester arsenic(III) ions in condition of acute arsenic toxicity. Toxicology 2016; 366-367:68-73. [PMID: 27523482 DOI: 10.1016/j.tox.2016.08.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/06/2016] [Accepted: 08/08/2016] [Indexed: 12/18/2022]
Abstract
The major cause of toxicity of trivalent arsenicals is due to their interaction with the sulfhydryl groups in proteins. Because of its high content, Metallothionein (MT) provides one of the most favorable conditions for the binding of As(III) ions to it. MT has long been anticipated for providing resistance in case of arsenic (As) toxicity with similar mechanism as in case of cadmium toxicity. The present study investigates whether the sequestration of As ions by MT is one of the mechanisms in providing protection against acute arsenic toxicity. A rat model study on the metal stoichiometric analysis of MT1 isoform isolated from the liver of arsenic treated, untreated and zinc treated animals has been carried out using the combination of particle induced X-ray emission (PIXE) and electrospray ionisation mass spectrometry (ESI-MS). The results revealed the absence of arsenic bound MT1 in the samples isolated from arsenic treated animals. Although, both Cu and Zn ions were present in MT1 samples isolated from all the treatment groups. Moreover, only partially metallated MT1 with varying number of Zn ions were observed in all the groups. These results suggest that the role of MT during acute arsenic toxicity is different from its already established role in case of cadmium toxicity.
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