Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes
Copyright policy )Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes
Acute ethanol exposure induces oxidative stress and apoptosis in primary rat hepatocytes. Previous data indicate that the mitochondrial permeability transition (MPT) is essential for ethanol-induced apoptosis. However, the mechanism by which ethanol induces the MPT remains unclear. In this study, we investigated the role of Bax, a proapoptotic Bcl-2 family protein, in acute ethanol-induced hepatocyte apoptosis. We found that Bax translocates from the cytosol to mitochondria before mitochondrial cytochrome c release. Bax translocation was oxidative stress dependent. Mitochondrial Bax formed a protein complex with the mitochondrial voltage-dependent anion channel (VDAC). Prevention of Bax-VDAC interactions by a microinjection of anti-VDAC antibody effectively prevented hepatocyte apoptosis by ethanol. In conclusion, these data suggest that Bax translocation from the cytosol to mitochondria leads to the subsequent formation of a Bax-VDAC complex that plays a crucial role in acute ethanol-induced hepatocyte apoptosis.
- Keio University Japan
- National Defense Medical College Japan
Male, Cell Membrane Permeability, Ethanol, Microinjections, Immunoblotting, Cytochromes c, Apoptosis, Mitochondria, Liver, In Vitro Techniques, Immunohistochemistry, Ion Channels, Electrophysiology, Oxidative Stress, Cross-Linking Reagents, Caspases, Cyclosporine, Hepatocytes, Animals, Ion Channel Gating, Immunosuppressive Agents
Male, Cell Membrane Permeability, Ethanol, Microinjections, Immunoblotting, Cytochromes c, Apoptosis, Mitochondria, Liver, In Vitro Techniques, Immunohistochemistry, Ion Channels, Electrophysiology, Oxidative Stress, Cross-Linking Reagents, Caspases, Cyclosporine, Hepatocytes, Animals, Ion Channel Gating, Immunosuppressive Agents
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