BRAIN MITOCHONDRIAL CYTOCHROMES P450 - XENOBIOTIC METABOLISM, PRESENCE OF MULTIPLE FORMS AND THEIR SELECTIVE INDUCIBILITY
BRAIN MITOCHONDRIAL CYTOCHROMES P450 - XENOBIOTIC METABOLISM, PRESENCE OF MULTIPLE FORMS AND THEIR SELECTIVE INDUCIBILITY
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DOI：
10.1006/abbi.1995.1344
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发表时间：
1995-06-20
影响因子：
3.9
通讯作者：
RAVINDRANATH, V
中科院分区：
文献类型：
--
作者：
BHAGWAT, SV;BOYD, MR;RAVINDRANATH, V
检测了大鼠脑线粒体代谢多种外源物质的能力。对分离的大鼠脑线粒体中细胞色素P450(P450)的存在及其相关的单加氧酶活性进行了评估，并与微粒体中的相应活性进行了比较。幼龄大鼠脑线粒体中的总P450含量是相应微粒体水平的两倍。脑线粒体代谢强致癌物N-亚硝基二甲胺的能力是相应微粒体活性的两倍多，而7-乙氧基香豆素-O-脱乙基酶的活性显著低于线粒体。用纯化的大鼠肝微粒体P450(2B1/2B2)、P450LA1和P4502E1以及纯化的苯巴比妥诱导的大鼠脑P450的抗血清进行免疫印迹实验，发现在分离的脑线粒体中存在免疫反应条带。这些不同的P450抗体对大脑线粒体单加氧酶活性有显著的抑制作用，尽管程度不同。在线粒体NADPH细胞色素P450还原酶中加入抗血清，不影响线粒体P450相关单加氧酶的活性，但能完全抑制相应的单加氧酶活性。慢性乙醇染毒引起脑线粒体P450总含量和已知P4502E1介导的单加氧酶活性的双重诱导，如N-亚硝基二甲胺-N-脱甲基酶和对-硝基苯酚羟基酶。苯巴比妥预处理可诱导脑线粒体氨基比林N-脱甲基酶的活性。这项研究证明了大鼠脑线粒体中存在多种形式的P450，它们的诱导性，以及它们代谢外源物质的能力。(C)1995年学术出版社。
The capability of rat brain mitochondria to metabolize a variety of xenobiotics was examined. The presence of cytochrome P450 (P450) and associated monooxygenase activities were estimated in isolated rat brain mitochondria and compared with the corresponding activities in microsomes. Total P450 content in brain mitochondria from naive rats was twice that of the corresponding microsomal level. The ability of brain mitochondria to metabolize the potent carcinogen N-nitrosodimethylamine was more than twofold that of the corresponding microsomal activity, while the 7-ethoxycoumarin-O-deethylase activity was significantly lower in mitochondria. Immunoblot experiments using antisera to purified rat liver microsomal P450s, namely P450 (2B1/2B2), P450LA1, and P4502E1, and purified phenobarbital-inducible rat brain P450, revealed the presence of immunoreactive bands in isolated brain mitochondria. These various antibodies to P450 inhibited the brain mitochondrial monooxygenase activities to significant, though varying extent. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450 associated monooxygenase activities, although it completely inhibited the corresponding microsomal activities. Chronic ethanol administration resulted in twofold induction of total P450 content and the monooxygenase activities known to be mediated by P4502E1, such as N-nitrosodimethylamine-N-demethylase and p-nitrophenol hydroxylase in brain mitochondria. Pretreatment of animals with phenobarbital resulted in the induction of aminopyrine N-demethylase activity in brain mitochondria. The study demonstrates the presence of multiple forms of P450 in the rat brain mitochondria, their inducibility, and their capability to metabolize xenobiotics. (C) 1995 Academic Press, Inc.