Pyridine induction of cytochrome P-450 in the rat: role of P-450j (alcohol-inducible form) in pyridine N-oxidation.
Pyridine induction of cytochrome P-450 in the rat: role of P-450j (alcohol-inducible form) in pyridine N-oxidation.
复制标题
DOI：
--
复制
发表时间：
1988-09
期刊：
影响因子：
--
通讯作者：
Sang Geon Kim;David E. Williams;E. Schuetz;P. Guzelian;R. Novak
中科院分区：
文献类型：
--
作者：
Sang Geon Kim;David E. Williams;E. Schuetz;P. Guzelian;R. Novak
先前的研究表明，吡啶（PY）预处理提高了兔肝微粒体总细胞色素P-450的含量，这与微粒体电泳模式中P-450LM4和LM3区域出现强条带有关，并增加了PY n -氧化物的产生和n -亚硝基二甲胺、酒精和苯胺代谢的速度。本研究发现，与对照组相比，给予大鼠PY （100mg /kg， 4天）可使肝微粒体细胞色素P-450含量升高约2.5倍。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示，在P-450j（乙醇诱导的大鼠肝细胞色素P-450的主要形式）区域有一个增强迁移强度的蛋白带。免疫化学分析证实，与对照、苯巴比妥或β -萘黄酮诱导的动物制剂相比，py诱导的微粒体中免疫反应性P-450j蛋白水平升高。PY诱导的微粒体产生PY n -氧化物的速率比未处理的对照组提高了4倍，比苯巴比妥或β -萘黄酮诱导的微粒体高约1.5至2倍。当数据归一化以增加P-450含量时，表明py诱导微粒体的底物特异性改变。对硝基酚羟化酶活性主要由乙醇诱导形式的P-450表现出来，在py诱导的微粒体中，相对于未诱导的微粒体，对硝基酚羟化酶活性提高了约4倍，当每纳米摩尔P-450表达时，在py诱导的制剂中，与苯巴比妥、β -萘黄酮诱导或未诱导的微粒体相比，对硝基酚羟化酶活性提高了约2至3倍。（摘要删节250字）
Previous research has shown that pyridine (PY) pretreatment of rabbits elevates total hepatic microsomal cytochrome P-450 content in association with the appearance of intense bands in the region of P-450LM4 and LM3 in the electrophoretic pattern of the microsomes and increased rates of PY N-oxide production and N-nitrosodimethylamine, alcohol and aniline metabolism. In the present study, PY administration (100 mg/kg i.p., 4 days) to rats was found to elevate hepatic microsomal cytochrome P-450 content approximately 2.5-fold as compared to controls. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed a protein band of enhanced intensity migrating in the region of P-450j, the major ethanol-inducible form of rat liver cytochrome P-450. Immunochemical analysis confirmed that the level of immunoreactive P-450j protein was increased in PY-induced microsomes as compared to preparations from control, phenobarbital- or beta-naphthoflavone-induced animals. The rate of PY N-oxide production was enhanced 4-fold in PY-induced microsomes relative to untreated controls and was approximately 1.5- to 2-fold greater than that monitored for either phenobarbital- or beta-naphthoflavone-induced microsomes. When data were normalized for increased P-450 content, an altered substrate specificity was suggested for the PY-induced microsomes. para-Nitrophenol hydroxylase activity, which is exhibited primarily by the ethanol-inducible form of P-450, was elevated approximately 4-fold in PY-induced microsomes relative to uninduced microsomes and, when expressed per nanomol of P-450, was approximately 2- to 3-fold greater in PY-induced preparations as compared to phenobarbital-, beta-naphthoflavone-induced, or uninduced microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)