title: Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.
abstract: Mercury is a well-known toxic metal, which induces oxidative stress. Pancreatic beta-cells are vulnerable to oxidative stress. The pathophysiological effect of mercury on the function of pancreatic beta-cells remains unclear. The present study was designed to investigate the effects of methylmercury (MeHg)-induced oxidative stress on the cell viability and function of pancreatic beta-cells. The number of viable cells was reduced 24 h after MeHg treatment in a dose-dependent manner with a range from 1 to 20 microM. 2',7'-Dichlorofluorescein fluorescence as an indicator of reactive oxygen species (ROS) formation after exposure of HIT-T15 cells or isolated mouse pancreatic islets to MeHg significantly increased ROS levels. MeHg could also suppress insulin secretion in HIT-T15 cells and isolated mouse pancreatic islets. After 24 h of exposure to MeHg, HIT-T15 cells had a significant increase in mercury levels with a dose-dependent manner. Moreover, MeHg displayed several features of cell apoptosis including an increase of the sub-G1 population and annexin-V binding. Treatment of HIT-T15 cells with MeHg resulted in disruption of the mitochondrial membrane potential and release of cytochrome c from the mitochondria to the cytosol and activation of caspase-3. Antioxidant N-acetylcysteine effectively reversed the MeHg-induced cellular responses. Altogether, our data clearly indicate that MeHg-induced oxidative stress causes pancreatic beta-cell apoptosis and dysfunction.
authors.affiliation: Institute of Toxicology, Department of Laboratory Medicine, and Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Chun Fa
authors.initials: CF
authors.lastname: Huang
authors.forename: Keh Sung
authors.initials: KS
authors.lastname: Tsai
authors.forename: Rong Sen
authors.initials: RS
authors.lastname: Yang
authors.forename: Cheng Chieh
authors.initials: CC
authors.lastname: Yen
authors.forename: Ching Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Shoei Yn
authors.initials: SY
authors.lastname: Lin-Shiau
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D004785:Environmental Pollutants; D007328:Insulin; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases