Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver.

摘要: Abstract Background . Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor apoptotic cell death localized mainly inner mitochondrial membrane crista, purpose this study was to determine whether cell-specific changes levels could account for hypoxia-induced SECs. Materials methods A low-flow model generated isolated reducing perfusate inflow pressure from 10 2.5 cmH 2 O h. Apoptosis then evaluated using TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial protein were determined SECs cryosectioning immunogold labeling electron microscopy. Results TUNEL-positive nonparenchymal cells, identified as SECs, observed predominantly hypoxic livers, whereas few parenchymal stained. higher than under control conditions, but they declined significantly during hypoxia, though no morphological signs apparent. In hepatocytes, contrast, unaffected hypoxia. Pretreatment with specific oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5- ]-1,3,5-triazine-4-olate monohydrate, which blocks peroxide, also blocked both decline Conclusion Hydrogen peroxide-dependent declines induce liver.