It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury;however the underlying mechanisms remain unknown.In this paper,we demonstrated that primary hepatocytes from...It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury;however the underlying mechanisms remain unknown.In this paper,we demonstrated that primary hepatocytes from transgenic 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 to a 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 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 partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.Cellular & Molecular Immunology. 2005;2(1):40-48.展开更多
文摘It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury;however the underlying mechanisms remain unknown.In this paper,we demonstrated that primary hepatocytes from transgenic 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 to a 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 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 partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.Cellular & Molecular Immunology. 2005;2(1):40-48.
