Inhibition for the Low Flow Hypoxia-Induced Mitochondrial Dysfunction using Methylprednisolone and Bcl-2

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1 Bcl-2 localizationBcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. We report that Bcl-2 is expressed in normal rat liver, and located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.2 The hypoxia-induced mitochondrial Bcl-2 declineThe apoptotic nonparenchymal cells, identified as SECs, were observed, predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchyma! ceils were stained. Mitochondrial Bcl-2 levels declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. Pretreatment with a specific xanthine oxidase inhibitor blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.3 The mechanism by which methyiprednisolone protects the ischermic liverPretreatment with 30 mg/kg, 10mg/kg or 3 mg/kg methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization, and enzyme leakage, though hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. The beneficial effect of methylprednisolone appears to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.