Pancreatic β-cell dysfunction is a prerequisite for the development of type 2 diabetes. Alcoholism is a diabetes risk factor and ethanol increases oxidative stress in β-cells, whereas the mitochondrial chaperone prohibitin (PHB) has antioxidant effects in several cell types.
In the present study we investigated whether PHB is expressed in β-cells and protects these cells against deleterious effects of ethanol, using INS-1E and RINm5F β-cell lines.
In ethanol-treated cells, MTT reduction and ATP production decreased, whereas reactive oxygen species, uncoupling protein 2 and cleaved caspase-3 levels increased. In addition, flow cytometry analysis showed an increase of apoptotic cells. Ethanol treatment increased PHB expression and induced PHB translocation from the nucleus to the mitochondria. PHB overexpression decreased the apoptotic effects of ethanol, whereas PHB knockdown enhanced these effects. The protective effects of endogenous PHB were recapitulated by incubation of the cells with recombinant human PHB.
Thus, PHB is expressed in β-cells, increases with oxidative stress and protects the cells against deleterious effects of ethanol.
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