Acetone-regulated synthesis and degradation of cytochrome P4502E2 and cytochrome P4502B1 in rat liver
Acetone-regulated synthesis and degradation of cytochrome P4502E2 and cytochrome P4502B1 in rat liver
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丙酮调节大鼠肝脏细胞色素 P4502E2 和细胞色素 P4502B1 的合成和降解
DOI：
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
M. Ingelman
中科院分区：
文献类型：
--
作者：
M. Ronis;I. Johansson;K. Hultenby;J. Lagercrantz;H. Glaumann;M. Ingelman
通过单次灌胃丙酮后0、6、12、24、48和96小时大鼠肝脏中脱辅基蛋白的mRNA水平、催化活性和亚细胞分布来研究CYP2E1和2B1的调节。丙酮处理后的任何时间都没有观察到肝脏 CYP2E1 mRNA 水平的变化，而微粒体中 CYP2E1 蛋白的量以及 CYP2E1 催化的 4-硝基苯酚羟化酶和四氯化碳引发的脂质过氧化活性则观察到快速上升。然而，CYP2E1 依赖性催化活性比免疫可检测的 CYP2E1 蛋白下降得快得多，表明这种细胞色素 P-450 在降解之前已失活。在原代肝细胞培养物中也观察到类似的结果。相比之下，在相同的微粒体制剂中观察到 CYP2B1 和 CYP2B1 依赖性戊氧基试卤灵 O-去戊基化水平的伴随变化。通过溶酶体中蛋白质的免疫定量和免疫组织化学研究 CYP2E1 和 CYP2B1 的降解机制，表明它们通过自噬溶酶体途径降解。数据表明，CYP2E1 在内质网中急剧失活，并且该同工酶的降解至少部分通过溶酶体途径发生。相比之下，CYP2B1 主要在合成水平上受到控制。
The regulation of CYP2E1 and 2B1 was studied by following mRNA levels, catalytic activities and the subcellular distribution of the apoproteins in rat liver 0, 6, 12, 24, 48 and 96 h after a single intragastric dose of acetone. No changes were observed in hepatic CYP2E1 mRNA levels at any time after acetone treatment, whereas rapid rises were observed in the microsomal amount of CYP2E1 protein and CYP2E1-catalyzed 4-nitrophenol hydroxylase and carbon-tetrachloride-initiated lipid-peroxidation activities. However, CYP2E1-dependent catalytic activities declined much faster than the immunodetectable CYP2E1 protein, suggesting that this cytochrome P-450 is inactivated prior to degradation. Similar results were seen in primary hepatocyte cultures. By contrast, concomitant changes in levels of CYP2B1 and CYP2B1-dependent O-depentylation of pentoxyresorufin were observed in the same microsomal preparations. Investigation of the degradative mechanism of both CYP2E1 and CYP2B1 by immunoquantitation of the proteins in lysosomes and by immunohistochemistry indicated their degradation via an autophagic-lysosomal pathway. The data suggest that CYP2E1 is acutely inactivated in the endoplasmic reticulum and that degradation of this isozyme occurs, at least in part, by the lysosomal route. By contrast, CYP2B1 is principally controlled at the level of synthesis.
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影响因子：
3.6
作者：
D. Heuman;E. J. Gallagher;J. Barwick;N. Elshourbagy;P. Guzelian
通讯作者：
D. Heuman;E. J. Gallagher;J. Barwick;N. Elshourbagy;P. Guzelian
影响因子：
3.9
作者：
LUBET, RA;MAYER, RT;GUENGERICH, FP
通讯作者：
GUENGERICH, FP
核糖核酸酶 A 和核糖核酸酶 S 蛋白显微注射到人成纤维细胞胞浆中的溶酶体降解。
DOI：
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发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
McElligott,MA;Miao,P;Dice,JF
通讯作者：
Dice,JF
影响因子：
3.6
作者：
D. Koop
通讯作者：
D. Koop
二乙醚作为丙酮/乙醇诱导型细胞色素 P-450 的底物和细胞色素 P-450 的诱导剂。
影响因子：
3.6
作者：
Brady,JF;Lee,MJ;Li,M;Ishizaki,H;Yang,CS
通讯作者：
Yang,CS