Identification of the cyanopregnenolone-inducible form of hepatic cytochrome P-450 as a catalyst of aldrin epoxidation.
Identification of the cyanopregnenolone-inducible form of hepatic cytochrome P-450 as a catalyst of aldrin epoxidation.
复制标题
鉴定氰基孕烯醇酮诱导形式的肝细胞色素 P-450 作为艾氏剂环氧化催化剂。
DOI：
10.1016/0006-2952(83)90477-x
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发表时间：
1983
影响因子：
5.8
通讯作者：
Guzelian,PS
中科院分区：
文献类型：
--
作者：
Newman,SL;Guzelian,PS
鉴于最近有研究表明，肝微粒体乙醇蛋白的氧化活性选择性地反映了苯巴比妥(PB)诱导的细胞色素P-450(P-450PB)形式(S)，我们测试了孕烯醇酮-16α-碳腈(PCN)的作用，这是一种合成类固醇，可诱导P-450PCN，一种在生化和免疫化学上与P-450PB相区别的细胞色素。在给予PB、3-MC或PCN的大鼠肝微粒体中，后者比PB更能提高艾氏剂环氧化活性，而3-MC则降低酶活性。此外，针对P-450PCN或P-450PB的形式特异性抗体可选择性地抑制PCN或PB处理的大鼠微粒体的艾氏剂环氧化活性，而抗P-450MC抗体对诱导动物或对照动物制备的微粒体无抑制作用。我们得出结论，P-450PCN，P-450PB，可能还有其他细胞色素P-450催化艾氏剂环氧化，排除了该酶作为单一形式细胞色素的特异性标志物的可能性。
In light of recent suggestions that hepatic microsomal aldrin expoxidation activity selectively reflects the phenobarbital (PB)-inducible form(s) of cytochrome P-450 (P-450PB), we tested the effect of pregnenolone-16α-carbonitrile (PCN), a synthetic steroid that induces P-450PCN, a form of the cytochrome biochemically and immunochemically distinguishable from P-450PB. In hepatic microsomes prepared from rats receiving PB, 3-methylcholanthrene (3-MC), or PCN, the latter compound produced a greater increase in aldrin epoxidation activity relative to control than did PB, whereas 3-MC decreased enzyme activity. Moreover, the aldrin epoxidation activity in microsomes prepared from PCN- or PB-pretreated rats was selectively inhibited by form-specific antibodies directed against P-450PCNor P-450PB, respectively, whereas anti-P-450MCantibodies gave no inhibition with microsomes prepared from induced or control animals. We conclude that P-450PCN, P-450PB, and probably other cytochromes P-450 catalyze aldrin epoxidation, precluding use of this enzyme as a specific marker of a single form of the cytochrome.