Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice.
Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice.
复制标题
苯巴比妥在芳烃反应性和非反应性小鼠肝脏中诱导 CYP1A2。
DOI：
--
复制
发表时间：
1999
影响因子：
3.9
通讯作者：
Nobuo Nemoto
中科院分区：
文献类型：
--
作者：
T. Sakuma;Miwako Ohtake;Yoko Katsurayama;K. Jarukamjorn;Nobuo Nemoto
研究了苯巴比妥处理对不同品系小鼠肝脏细胞色素P-450（CYP 1A 2）酶表达的影响。苯巴比妥在芳烃响应性[C57 BL/6 NCrj（C57 BL/6）、C3 H/HeJSlc]和非响应性（DBA/2NCrj、AKR/JSea、NZB/NSlc）小鼠品系中，在mRNA、蛋白质和酶活性水平（甲氧基试卤灵O-去甲基化和2-氨基-3-甲基咪唑[4，5-f]喹啉的代谢活化）诱导CYP 1A 2表达。CYP 2B 10（在小鼠中被称为苯巴比妥诱导型P-450）的诱导在所有5种供试品系的肝脏中均显著，而在雌性C57 BL/6和雌性DBA/2NCrj小鼠中未观察到对P-450 CYP 2B 9的明显诱导作用。这些结果表明，CYP 1A 2是小鼠中苯巴比妥诱导基因家族的成员，并表明芳香烃受体依赖性诱导途径不参与CYP 1A 2的诱导。这一概念与其他实验室最近使用AhR基因敲除小鼠提出的概念一致。以下是本报告的新意见。在这三个水平之间，CYP 1A 2 mRNA、蛋白质和酶活性的增加幅度相当（范围为1.4- 3. 1倍），表明苯巴比妥对CYP 1A 2的诱导主要在翻译前水平确定。环巴比妥、戊巴比妥和司可巴比妥也可诱导C57 BL/6小鼠原代培养肝细胞中的CYP 1A 2 mRNA。而巴比妥对CYP 1A 2 mRNA没有明显的诱导作用。
The effects of phenobarbital treatment on the expression of the cytochrome P-450 (CYP or P-450) enzyme CYP1A2 in the livers of mice of various strains were examined. Phenobarbital induced the expression of CYP1A2 at the levels of mRNA, protein, and enzyme activity (methoxyresorufin O-demethylation and metabolic activation of 2-amino-3-methylimidazo[4,5-f]quinoline) in both aryl hydrocarbon-responsive [C57BL/6NCrj (C57BL/6), C3H/HeJSlc] and -nonresponsive (DBA/2NCrj, AKR/JSea, NZB/NSlc) mouse strains. The induction of CYP2B10, which is known as a phenobarbital-inducible P-450 in mice, was prominent in the livers of all five strains examined, whereas clear inductive effects on the P-450 CYP2B9 were not observed in female C57BL/6 and female DBA/2NCrj mice. These results indicate that CYP1A2 is a member of the family of phenobarbital-inducible genes in mice and suggest that the aryl hydrocarbon receptor-dependent induction pathway is not involved in the induction of CYP1A2. This concept is in accordance with those proposed by other laboratories recently using the AhR knockout mice. The following are new observations of this report. The magnitude of the increases in the CYP1A2 mRNA, protein, and enzyme activities were comparable among these three levels (ranging from 1.4- to 3. 1-fold), suggesting that the induction of CYP1A2 by phenobarbital is mainly determined at a pretranslational level. Cyclobarbital, pentobarbital, and secobarbital also induced CYP1A2 mRNA in primary culture hepatocytes from C57BL/6 mice. Barbital, in contrast, did not show any clear inductive effect on CYP1A2 mRNA.
DOI：
--
发表时间：
1995
期刊：
Princess Takamatsu symposia
影响因子：
--
作者：
Boobis,AR;Gooderham,NJ;Rich,KJ;Zhao,K;Edwards,RJ;Murray,BP;Lynch,AM;Murray,S;Davies,DS
通讯作者：
Davies,DS
一种巴比妥调节蛋白，与啮齿动物和细菌的细胞色素 P450 基因中的共同序列结合。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
He,JS;Fulco,AJ
通讯作者：
Fulco,AJ
对照和苯巴比妥诱导的大鼠肝细胞原代培养物中细胞色素 P-450 同工酶的表达和代谢活性。
影响因子：
3.9
作者：
Turner,NA;Wilson,NM;Jefcoate,CR;Pitot,HC
通讯作者：
Pitot,HC