Low-level sodium arsenite induces apoptosis through inhibiting TrxR activity in pancreatic β-cells.
In our previous study, we reported that sodium arsenite induced ROS-dependent apoptosis through lysosomal-mitochondrial pathway in pancreatic β-cells. Since the thioredoxin (Trx) system is the key antioxidant factor in mammalian cells, we investigate whether the inhibition of Trx system contributes to sodium arsenite-induced apoptosis in this study. After treatment with low-level (0.25-1μM) sodium arsenite for 96h, the thioredoxin reductase (TrxR) activity was decreased significantly in pancreatic INS-1 cells. Following with the inactivation of TrxR, ASK1 was released from combining with Trx, which was evidenced by increased levels of ASK1 in sodium arsenite-treated INS-1 cells. Subsequently, activated ASK1 accelerated the expression of proapoptotic protein Bax and reduced the expression of anti-apoptic protein Bcl-2. Finally, low-level sodium arsenite induced apoptosis via caspase-3 in INS-1 cells. Knockdown of ASK1 alleviated sodium arsenite-induced apoptosis. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, inactivation of Trx system might provide insights into the underlying mechanisms at the environmental exposure levels.
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Xiao-Feng
XF
Yao
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Bai-Lu
BL
Zheng
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Jie
J
Bai
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Li-Ping
LP
Jiang
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Yue
Y
Zheng
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Bao-Xu
BX
Qi
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Cheng-Yan
CY
Geng
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Lai-Fu
LF
Zhong
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Guang
G
Yang
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Min
M
Chen
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Xiao-Fang
XF
Liu
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China; Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China. Electronic address: sunxiance@gmail.com.
Xian-Ce
XC
Sun
D000818:Animals; D017209:Apoptosis; D018053:Arsenites / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D017670:Sodium Compounds / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
D018053:Arsenites; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; C017947:sodium arsenite; D013880:Thioredoxin-Disulfide Reductase; D020930:MAP Kinase Kinase Kinases
ASK1; Apoptosis; INS-1 cells; Sodium arsenite; TrxR