Prohibitin protects against hypoxia-induced H9c2 cardiomyocyte cell death.

We recently demonstrated that short time exposure to hypoxia (15 min) in H9c2 cardiomyocytes protected cells against cell death, and longer exposure to hypoxia induced cell death. To understand the molecular mechanism concerning cell death and survival, it is intriguing to identify survival factors against cell death. Using proteomics analysis, levels of proteins derived from H9c2 cells exposed to hypoxia and normoxia were compared and candidates for survival factor were identified. One of the candidates was a prohibitin. Overexpression of prohibitin inhibited H9c2 cell death induced by hypoxia for longer hours. We further clarified the mechanism of cell death. Overexpression of prohibitin inhibited decrease of mitochondrial membrane potential levels, decrease of Bcl-2 level in mitochondria and cytochrome c release to cytosol from mitochondria induced by hypoxia. The mechanism for survival was that overexpression of prohibitin inhibited cytochrome c release by decrease of mitochondrial membrane potential levels and decrease of Bcl-2 level. Taken together, identified prohibitin may function as a survival factor against hypoxiainduced cell death.