These authors contributed equally to this work.
Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells
Article first published online: 31 JUL 2014
Copyright © 2014 Wiley Periodicals, Inc.
How to Cite
Pan, X., Jiang, L., Zhong, L., Geng, C., Jia, L., Liu, S., Guan, H., Yang, G., Yao, X., Piao, F. and Sun, X. (2014), Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells. Environ. Toxicol.. doi: 10.1002/tox.22027
- Article first published online: 31 JUL 2014
- Manuscript Accepted: 13 JUL 2014
- Manuscript Revised: 6 JUL 2014
- Manuscript Received: 26 JAN 2014
- The National Natural Science Foundation of China (NSFC). Grant Numbers: 30972562, 30600488
- Program for Liaoning Excellent Talents in University (LNET). Grant Number: LJQ2011096
- Liaoning BaiQianWan Talents Program. Grant Number: 2009921030
Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.