Related Experiment Video
Updated: Apr 5, 2026
Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Low-level sodium arsenite induces apoptosis through inhibiting TrxR activity in pancreatic β-cells
Xiao-Feng Yao1, Bai-Lu Zheng1, Jie Bai1
1Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Abstract:
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.
Insights
Low-level sodium arsenite exposure inhibits the thioredoxin (Trx) system, leading to pancreatic cell apoptosis via the ASK1-caspase-3 pathway. This arsenic-induced cell death mechanism offers insights into diabetes pathogenesis.
Area of Science:
- Cell Biology
- Toxicology
- Endocrinology
Background:
- Sodium arsenite induces apoptosis in pancreatic beta-cells via a ROS-dependent, lysosomal-mitochondrial pathway.
- The thioredoxin (Trx) system is a critical antioxidant defense in mammalian cells.
Purpose of the Study:
- To investigate if inhibiting the Trx system contributes to sodium arsenite-induced apoptosis in pancreatic INS-1 cells.
- To elucidate the molecular mechanisms linking low-level arsenic exposure to pancreatic cell dysfunction.
Main Methods:
- Pancreatic INS-1 cells were treated with low-level sodium arsenite (0.25-1μM) for 96 hours.
- Assessed thioredoxin reductase (TrxR) activity, ASK1 release, and expression of apoptosis-related proteins (Bax, Bcl-2).
- Investigated the role of ASK1 using knockdown experiments and caspase-3 activation.
Main Results:
- Sodium arsenite significantly decreased TrxR activity in INS-1 cells.
- TrxR inactivation led to ASK1 release and subsequent upregulation of Bax and downregulation of Bcl-2.
- Activated ASK1 promoted apoptosis via caspase-3, and ASK1 knockdown mitigated this effect.
Conclusions:
- Low-level sodium arsenite induces apoptosis in pancreatic beta-cells by inhibiting the Trx system and activating the ASK1-Bax/Bcl-2-caspase-3 pathway.
- Trx system inactivation offers a potential molecular mechanism for arsenic's role in diabetes development.
- Understanding these pathways is crucial for addressing environmental exposure risks related to diabetes.
