Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.
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.
Chen
Ya Wen
YW
Institute of Toxicology, Department of Laboratory Medicine, and Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Huang
Chun Fa
CF
Tsai
Keh Sung
KS
Yang
Rong Sen
RS
Yen
Cheng Chieh
CC
Yang
Ching Yao
CY
Lin-Shiau
Shoei Yn
SY
Liu
Shing Hwa
SH
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
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