The effect of ethanol-induced cytochrome p4502E1 on the inhibition of proteasome activity by alcohol.
The present investigation was undertaken to determine the effect of CYP2E1 induction by ethanol on the inhibition of proteasomal activity in wild-type and CYP2E1 knockout C57 black mice. The proteasomal chymotrypsin-like activity decreased significantly in ethanol-fed wild-type mice liver, but was not reduced in ethanol-fed knockout mice liver. The 26S proteasomal activity was decreased more by ethanol feeding than was the 20S proteasomal fraction. Individual hepatocytes lost immunostaining of the proteasomes in the centrilobular zone in the livers of ethanol-fed wild-type mice and the knockout mouse liver. There was increased product of protein oxidation in the liver in the wild type but not in the knockout mice given ethanol. Taken together, these results suggest that CYP2E1 induction was responsible for the decrease in proteasome activity seen in the wild-type mice which head to the accumulation of oxidized proteins which were increased as the result of free radicals generated by CYP2E1 metabolism of ethanol.
Bardag-Gorce
F
F
Department of Pathology, Harbor UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509, USA.
Yuan
Q X
QX
Li
J
J
French
B A
BA
Fang
C
C
Ingelman-Sundberg
M
M
French
S W
SW
D000818:Animals; D003546:Cysteine Endopeptidases; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D046988:Proteasome Endopeptidase Complex
D009097:Multienzyme Complexes; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex