Huang TT, Sun WJ, Liu HY, Ma HL, Cui BX. p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus. World J Diabetes 2021; 12(11): 1894-1907 [PMID: 34888014 DOI: 10.4239/wjd.v12.i11.1894]
Corresponding Author of This Article
Bao-Xia Cui, PhD, Chief Physician, Professor, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhua Xi Road, Jinan 250013, Shandong Province, China. cuibaoxia@sdu.edu.cn
Research Domain of This Article
Obstetrics & Gynecology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Nov 15, 2021; 12(11): 1894-1907 Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1894
p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus
Ting-Ting Huang, Wen-Juan Sun, Hai-Ying Liu, Hong-Li Ma, Bao-Xia Cui
Ting-Ting Huang, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
Ting-Ting Huang, Hong-Li Ma, Department of Obstetrics, Taian City Central Hospital, Taian 271000, Shandong Province, China
Wen-Juan Sun, Department of Obstetrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
Hai-Ying Liu, Department of Obstetrics and Gynecology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266000, Shandong Province, China
Bao-Xia Cui, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong Province, China
Author contributions: Huang TT, Sun WJ, Liu HY, and Cui BX designed and coordinated the study; Huang TT, Sun WJ, and Ma HL performed the experiments, acquired, and analyzed the data; Huang TT, Sun WJ, and Liu HY interpreted the data; Huang TT and Sun WJ wrote the manuscript; All authors approved the final version of the article.
Supported byThe Scientific Research Fund of Qilu Hospital (Qingdao), No. QDKY2015ZD04.
Institutional review board statement: The study was reviewed and approved by the Taian City Central Hospital Institutional Review Board (Approval NO. 2016-05-15).
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at cuibaoxia@sdu.edu.cn. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Xia Cui, PhD, Chief Physician, Professor, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhua Xi Road, Jinan 250013, Shandong Province, China. cuibaoxia@sdu.edu.cn
Received: July 22, 2021 Peer-review started: July 22, 2021 First decision: August 16, 2021 Revised: August 29, 2021 Accepted: September 19, 2021 Article in press: September 19, 2021 Published online: November 15, 2021 Processing time: 116 Days and 5.6 Hours
Abstract
BACKGROUND
Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM.
AIM
The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM.
METHODS
A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining.
RESULTS
The p66Shc mRNA level was increased in the serum (P < 0.01) and placentas (P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas (P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc (P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA (P < 0.05).
CONCLUSION
The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.
Core Tip: The role of placental mitochondria in the etiology of gestational diabetes mellitus (GDM) is an emerging area of research. In this study, we report the expression levels of dynamin-related protein 1 (Drp1) and p66Shc in GDM and in the JEG3 human trophoblast cell line. Increased expression of p66Shc was induced by high glucose-activated Drp1 and promoted overproduction of reactive oxygen species, which may be the primary cause of cell damage and apoptosis during the occurrence and development of GDM.
