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新生大鼠肝脏微粒体中细胞色素P - 450b/e和P - 450c的诱导及催化活性

Induction and catalytic activities of cytochromes P-450b/e and P-450c in the liver microsomes of neonatal rats.

作者信息

Gulyaeva L F, Mishin V M, Lyakhovich V V

出版信息

Int J Biochem. 1986;18(9):829-34. doi: 10.1016/0020-711x(86)90060-1.

DOI:10.1016/0020-711x(86)90060-1
PMID:3758464
Abstract

The activities of cytochrome P-450-dependent monooxygenases has been investigated in the liver microsomes of newborn rats (3-16 days after birth) induced with PB or 3-MC. It has been shown that the induction by PB and 3-MC results in the increase of both the total amount of cytochrome P-450 as determined by the CO-reduced spectrum and the amount of induced forms P-450b/e and P-450c respectively. In the course of induction of the specific forms of cytochrome P-450 BP-hydroxylase and 7-ER-O-deethylase activities increased at 3-MC-induction, while BPh-N-demethylase and BP-hydroxylase increased at PB-induction. Analysis of inhibition of monooxygenase reactions with antibodies has showed that only P-450c was involved in metabolism of BP and 7-ER. Participation of P-450b/e in BPh N-demethylation was notably lower in the neonates in comparison to the adult rats. In the one-week-old rats induced with 3-MC a considerable rate of BP hydroxylation and 7-ER O-deethylation (2-4.5 nmol of product min-1 mg-1) has been observed despite a small amount of P-450 (0.02-0.1 nmol/mg of protein). This fact shows the higher catalytic activity of this cytochrome P-450 in the neonates compared to similar characteristics of P-450c in the 3-MC-induced microsomes. Metabolism of BP in the PB-microsomes of the neonatal rats was inhibited neither by anti-P-450b/e nor anti-P-450c in contrast to the adults, where this reaction was inhibited by antibodies against P-450b/e.

摘要

已对用苯巴比妥(PB)或3 - 甲基胆蒽(3 - MC)诱导的新生大鼠(出生后3 - 16天)肝脏微粒体中细胞色素P - 450依赖的单加氧酶活性进行了研究。结果表明,PB和3 - MC诱导导致通过CO还原光谱测定的细胞色素P - 450总量增加,以及分别诱导的P - 450b/e和P - 450c形式的量增加。在细胞色素P - 450特定形式的诱导过程中,3 - MC诱导时BP - 羟化酶和7 - 乙氧基香豆素 - O - 脱乙基酶活性增加,而PB诱导时联苯 - N - 脱甲基酶和BP - 羟化酶增加。用抗体对单加氧酶反应抑制的分析表明,只有P - 450c参与BP和7 - 乙氧基香豆素的代谢。与成年大鼠相比,新生大鼠中P - 450b/e对联苯N - 脱甲基作用的参与明显较低。在用3 - MC诱导的一周龄大鼠中,尽管细胞色素P - 450含量少(0.02 - 0.1 nmol/毫克蛋白质),但仍观察到相当高的BP羟化率和7 - 乙氧基香豆素O - 脱乙基率(2 - 4.5 nmol产物/分钟·毫克 - 1)。这一事实表明,与3 - MC诱导的微粒体中P - 450c的类似特性相比,新生大鼠中这种细胞色素P - 450具有更高的催化活性。与成年大鼠不同,成年大鼠中该反应被抗P - 450b/e抗体抑制,新生大鼠PB微粒体中BP的代谢既不被抗P - 450b/e抗体也不被抗P - 450c抗体抑制。

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1
Induction and catalytic activities of cytochromes P-450b/e and P-450c in the liver microsomes of neonatal rats.新生大鼠肝脏微粒体中细胞色素P - 450b/e和P - 450c的诱导及催化活性
Int J Biochem. 1986;18(9):829-34. doi: 10.1016/0020-711x(86)90060-1.
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