Cadmium Induces Apoptosis in Pancreatic β-Cells through a Mitochondria-Dependent Pathway: The Role of Oxidative Stress-Mediated c-Jun N-Terminal Kinase Activation

doi:10.1371/journal.pone.0054374

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 職業安全衛生學系暨碩士班 > 博碩士論文 > Item 310902500/20400

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Title:	Cadmium Induces Apoptosis in Pancreatic β-Cells through a Mitochondria-Dependent Pathway: The Role of Oxidative Stress-Mediated c-Jun N-Terminal Kinase Activation
Authors:	Chang, Kai-Chih Hsu, Ching-Cheng Liu, Shing-Hwa Su, Chin-Chuan Yen, Cheng-Chieh Lee, Ming-Jye Chen, Kuo-Liang Ho, Tsung-Jung Hung, Dong-Zong Wu, Chin-Ching Lu, Tien-Hui Su, Yi-Chang Chen, Ya-Wen Huang, Chun-Fa
Contributors:	職業安全衛生學系
Date:	2013-02
Issue Date:	2019-10-24T03:09:48Z (UTC)
Publisher:	PLoS ONE
ISSN:	1932-6203
Abstract:	Cadmium (Cd), one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have suggested a possible link between Cd exposure and diabetes mellitus (DM). However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP) and the increase of cytosolic cytochrome c release), the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose) polymerase (PARP) cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK)1/2, and p38-mitogen-activated protein kinase (MAPK), which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA) transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580) did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/20400
Relation:	PLoS ONE, vol.8,issue 2, page e54374
Appears in Collections:	[職業安全衛生學系暨碩士班] 博碩士論文

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