title: Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.
abstract: Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes.
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Fu
authors.affiliation: The First Affiliated Hospital, China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Lu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, P.O. Box 249, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Qu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pi
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D006873:Hydroquinones / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C472829:1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole; D006873:Hydroquinones; D007093:Imidazoles; D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid; D006861:Hydrogen Peroxide; C018855:2-tert-butylhydroquinone; D010088:Oxidoreductases; D053148:Caspase 3; D005978:Glutathione