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It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury;howeverthe underlying mechanisms remain unknown.In this paper,we demonstrated that primary hepatocytes fromtransgenic mice overexpressing hepatitis B virus X protein(HBX)were more susceptible to ethanol- and TNF-α-induced apoptotic killing.Compared to normal control mouse hepatocytes,ethanol and/or TNF-α treatment led toa significant increase in reactive oxygen species,mitochondrial permeability transition,cytochrome C release,caspase-3 activity,and poly(ADP-ribose)polymerase degradation in hepatocytes from HBX transgenic mice.Blocking caspase-3 activity antagonized ethanol-and TNF-α-induced apoptosis in primary hepatocytes from HBXtransgenic mice.Taken together,our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol-and TNF-α-induced apoptosis by a caspase-3-dependent mechanism,which may partly explain the synergisticeffects of alcohol consumption and hepatitis B virus infection on liver injury.Cellular & Molecular Immunology.2005;2(1):40-48.
It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; howeverthe underlying mechanisms remain unknown.In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpress hepatitis B virus X protein (HBX) were more susceptible to ethanol- and TNF-α-induced apoptotic killing .Compared to normal control mouse hepatocytes, ethanol and / or TNF-α treatment led toa significant increase in reactive oxygen species, mitochondrial permeability transition, cytochrome C release, caspase-3 activity, and poly ribose) polymerase degradation in hepatocytes from HBX transgenic mice. Blocking caspase-3 activity antagonized ethanol-and TNF-α-induced apoptosis in primary hepatocytes from HBX transgenic mice. Taken together, our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol-and TNF -α-induced apoptosis by a caspase-3-dependent mechanism, which may partially explain the synergisticeffects of alcohol consumption and hepatitis B virus infection on liver injury. Cellular & Molecular Immunology. 2005; 2 (1): 40-48.