title: Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells.
abstract: 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 NH4 Cl 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.
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Xiao
authors: X
authors: Pan
authors: Natural Products Engineering Technology Research Center, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Liping
authors: L
authors: Jiang
authors: Natural Products Engineering Technology Research Center, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Laifu
authors: L
authors: Zhong
authors: Natural Products Engineering Technology Research Center, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Chengyan
authors: C
authors: Geng
authors: College of Laboratory Medicine, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Li
authors: L
authors: Jia
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Shuang
authors: S
authors: Liu
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Huai
authors: H
authors: Guan
authors: Natural Products Engineering Technology Research Center, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Guang
authors: G
authors: Yang
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Xiaofeng
authors: X
authors: Yao
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Fengyuan
authors: F
authors: Piao
authors: Department of Ocuupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.|Natural Products Engineering Technology Research Center, Dalian Medical University, No. 9 Western Section, Lvshun South Street, Dalian, 116044, People's Republic of China.
authors: Xiance
authors: X
authors: Sun
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005434:Flow Cytometry; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002843:Chromatin; D017382:Reactive Oxygen Species; D000643:Ammonium Chloride; D045304:Cytochromes c; D001151:Arsenic
keywords: INS-1cells; apoptosis; arsenic; lysosome; mitochondria