Bardag-Gorce F, Yuan Q X, Li J, French B A, Fang C, Ingelman-Sundberg M, French S W
Department of Pathology, Harbor UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509, USA.
Biochem Biophys Res Commun. 2000 Dec 9;279(1):23-9. doi: 10.1006/bbrc.2000.3889.
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.
本研究旨在确定乙醇诱导CYP2E1对野生型和CYP2E1基因敲除的C57黑小鼠蛋白酶体活性抑制的影响。蛋白酶体类胰凝乳蛋白酶样活性在乙醇喂养的野生型小鼠肝脏中显著降低，但在乙醇喂养的基因敲除小鼠肝脏中未降低。与20S蛋白酶体部分相比，乙醇喂养使26S蛋白酶体活性降低得更多。在乙醇喂养的野生型小鼠肝脏和基因敲除小鼠肝脏的中央小叶区，单个肝细胞失去了蛋白酶体的免疫染色。野生型小鼠给予乙醇后肝脏中蛋白质氧化产物增加，而基因敲除小鼠则未增加。综上所述，这些结果表明，CYP2E1的诱导是野生型小鼠中蛋白酶体活性降低的原因，这导致了氧化蛋白的积累，而氧化蛋白的增加是乙醇经CYP2E1代谢产生自由基的结果。
