Alterations of specific forms of cytochrome P-450 in rat liver during acute carbon tetrachloride intoxication.

Alterations of specific forms of cytochrome P-450 in rat liver during acute carbon tetrachloride intoxication.
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急性四氯化碳中毒期间大鼠肝脏中细胞色素 P-450 特定形式的变化。

DOI:
10.1016/0041-008x(81)90419-1
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发表时间:
1981
影响因子:
3.8
通讯作者:
Smuckler,EA
Smuckler,EA
中科院分区:
医学3区
文献类型:
--
作者:
Head,B;Moody,DE;Woo,CH;Smuckler,EA

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雄性大鼠以苯巴比妥、3-甲基胆蒽或相应的载药预处理,给予四氯化碳(CCl4), 3小时后处死。分离肝微粒体,测定细胞色素P-450含量和混合功能氧化酶活性。ccl4中毒后细胞色素P-450残留量在生理盐水和苯巴比妥预处理动物中相似。在用3-甲基胆蒽预处理后再用CCl4攻毒的动物中,细胞色素P-450的残留量显著增加。在盐水预处理的动物中,暴露于ccl4后,7-乙氧基香豆素的脱烷基反应减少,但苯丙胺或N,N-二甲苯胺的脱烷基反应没有减少。ccl4中毒后,苯巴比妥引起的脱烷基反应增强,而3-甲基胆蒽没有。微粒体用胆酸钠溶解;采用ω-辛胺- Sepharose 4B柱层析法部分纯化细胞色素P-450;采用sds -聚丙烯酰胺凝胶电泳分离细胞色素p -450。ccl4处理后,分子量为51,600的条带迁移的染色强度下降。此外,苯巴比妥诱导的成分(MW 51,600)也减少,但3-甲基胆蒽诱导后的成分(MW 57,900)没有减少。sds -聚丙烯酰胺凝胶电泳分离的微粒体蛋白和血红素染色的微粒体蛋白也显示出染色减少,其中苯巴比妥和生理盐水的微粒体蛋白比3-甲基胆碱诱导的微粒体蛋白更明显。这些数据表明,盐处理动物体内的特定细胞色素P-450(s)以及苯巴比妥诱导的细胞色素P-450(s),而不是3-甲基胆碱诱导的细胞色素P-450,容易受到ccl4诱导的破坏。
Male rats were pretreated with phenobarbital, 3-methylcholanthrene, or the corresponding vehicles, administered carbon tetrachloride (CCl4), and sacrificed 3 hr later. Hepatic microsomes were isolated and assayed for cytochrome P-450 content and mixed-function oxidase activity. The residual content of cytochrome P-450 after CCl4intoxication was similar in saline and phenobarbital-pretreated animals. Substantially greater amount of cytochrome P-450 remained in animals pretreated with 3-methylcholanthrene and then challenged with CCl4. In saline-pretreated animals, the dealkylation of 7-ethoxycoumarin, but not benzphetamine or N,N-dimethylaniline, was decreased following CCl4exposure. The enhanced dealkylation following phenobarbital, but not following by 3-methylcholanthrene, was also decreased after CCl4poisoning. Microsomes were solubilized with sodium cholate; cytochrome P-450 was partially purified by ω-octylamino Sepharose 4B column chromatography; and cytochrome P-450-containing elements were separated by SDS-polyacrylamide gel electrophoresis. A decrease in the staining intensity of a band migrating with a molecular weight of 51,600 was noted following CCl4treatment. Furthermore, the phenobarbital-induced component (MW 51,600), but not that appearing after 3-methylcholanthrene induction (MW 57,900), was also diminished. Microsomal proteins separated by SDS-polyacrylamide gel electrophoresis and stained for heme also showed a decrease in staining which was greater in those microsomal proteins from phenobarbital and saline than in 3-methylcholanthrene-induced animals. The data suggest that a specific cytochrome P-450(s) in the saline-treated animals as well as the cytochrome P-450(s) induced by phenobarbital, but not the 3-methylcholanthrene-induced cytochrome P-450, are susceptible to CCl4-induced destruction.
苯巴比妥和 3-甲基胆蒽预处理对 CCl 4 诱导的大鼠肝毒性的不同急性影响。
DOI: 10.1016/0041-008x(72)90180-9
发表时间: 1972
影响因子: 3.8
作者:
K. A. Suarez;G. Carlson;G. Fuller;N. Fausto
通讯作者: N. Fausto
DOI: --
发表时间: 1977
影响因子: 4.8
作者:
F. Guengerich
通讯作者: F. Guengerich
细胞色素P-450的分离纯化,以及多种形式的存在。
DOI: --
发表时间: 1979
影响因子: 13.5
作者:
F. Guengerich
通讯作者: F. Guengerich
DOI: 10.1042/bj0550416
发表时间: 1953-01-01
影响因子: 4.1
作者:
NASH, T
通讯作者: NASH, T
[92] 猪肝微粒体TPNH-细胞色素c还原酶的制备及性质
DOI: 10.1016/0076-6879(67)10098-0
发表时间: 1967
影响因子: --
作者:
B. Masters;C. Williams;H. Kamin
通讯作者: H. Kamin