Methylmercury induces pancreatic beta-cell apoptosis and dysfunction

Chem Res Toxicol. 2006 Aug;19(8):1080-5. doi: 10.1021/tx0600705.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Environmental Pollutants / toxicity*
  • Flow Cytometry
  • Insulin / metabolism
  • Insulin Secretion
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / physiology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology
  • Male
  • Membrane Potentials / drug effects
  • Methylmercury Compounds / toxicity*
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Annexin A5
  • Antioxidants
  • Environmental Pollutants
  • Insulin
  • Methylmercury Compounds
  • Reactive Oxygen Species
  • Cytochromes c
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases