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烯丙异丙基乙酰胺对苯巴比妥处理的家兔肝微粒体细胞色素P-450 2含量的体内和体外效应。

The effect in vivo and in vitro of allylisopropylacetamide on the content of hepatic microsomal cytochrome P-450 2 of phenobarbital treated rabbits.

作者信息

Liem H H, Johnson E F, Muller-Eberhard U

出版信息

Biochem Biophys Res Commun. 1983 Mar 29;111(3):926-32. doi: 10.1016/0006-291x(83)91388-8.

DOI:10.1016/0006-291x(83)91388-8
PMID:6838593
Abstract

Rabbits treated with phenobarbital were given a single injection of allylisopropylacetamide (AIA) s.c. and/or heme i.v. Hepatic microsomes were isolated 1, 5 and 24 hours post injection and the microsomal contents of both total cytochrome P-450 chromophore, and the protein moiety of P-450 2 were determined by spectrophotometric and immunochemical methods respectively. AIA caused the levels of total P-450 chromophore and of P-450 2 protein to decline to 30% of the control values at 5 hours post-injection. Concurrent administration of heme with AIA diminished the decrease in the total microsomal content of P-450 chromophore but not in that of P-450 2 protein. These findings suggest that the destruction of the heme prosthetic group of P-450 by suicide substrates such as AIA may lead to an enhanced degradation of the apo-P-450.

摘要

给用苯巴比妥治疗的兔子皮下注射一次烯丙异丙基乙酰胺(AIA)和/或静脉注射血红素。在注射后1、5和24小时分离肝微粒体,分别用分光光度法和免疫化学方法测定总细胞色素P-450发色团和P-450 2蛋白部分的微粒体含量。AIA导致注射后5小时总P-450发色团和P-450 2蛋白水平降至对照值的30%。血红素与AIA同时给药减少了P-450发色团微粒体总含量的下降,但没有减少P-450 2蛋白的下降。这些发现表明,自杀性底物如AIA对P-450血红素辅基的破坏可能导致脱辅基P-450的降解增强。

相似文献

1
The effect in vivo and in vitro of allylisopropylacetamide on the content of hepatic microsomal cytochrome P-450 2 of phenobarbital treated rabbits.烯丙异丙基乙酰胺对苯巴比妥处理的家兔肝微粒体细胞色素P-450 2含量的体内和体外效应。
Biochem Biophys Res Commun. 1983 Mar 29;111(3):926-32. doi: 10.1016/0006-291x(83)91388-8.
2
Structural and functional reconstitution of hepatic cytochrome P-450 in vivo. Reversal of allylisopropylacetamide-mediated destruction of the hemoprotein by exogenous heme.体内肝细胞色素P-450的结构与功能重建。外源性血红素逆转烯丙基异丙基乙酰胺介导的血蛋白破坏。
J Biol Chem. 1980 Nov 10;255(21):10128-33.
3
Inactivation of phenobarbital-inducible rabbit-liver microsomal cytochrome P-450 by allylisopropylacetamide: impact on electron transfer.烯丙异丙基乙酰胺对苯巴比妥诱导的兔肝微粒体细胞色素P-450的失活作用:对电子传递的影响
Biochim Biophys Acta. 1993 Apr 5;1142(1-2):74-82. doi: 10.1016/0005-2728(93)90086-u.
4
Formation of cytochrome P-450 containing haem or cobalt-protoporphyrin in liver homogenates of rats treated with phenobarbital and allylisopropylacetamide.用苯巴比妥和烯丙异丙基乙酰胺处理的大鼠肝脏匀浆中含血红素或钴原卟啉的细胞色素P - 450的形成。
Biochem J. 1984 Sep 1;222(2):453-62. doi: 10.1042/bj2220453.
5
Differential haemin-mediated restoration of cytochrome P-450 N-demethylases after inactivation by allylisopropylacetamide.烯丙基异丙基乙酰胺使细胞色素P-450 N-脱甲基酶失活后,血红素介导的差异性恢复
Biochem J. 1985 Apr 1;227(1):277-86. doi: 10.1042/bj2270277.
6
Exogenous heme restores in vivo functional capacity of hepatic cytochrome P-450 destroyed by allylisopropylacetamide.外源性血红素可恢复被烯丙异丙基乙酰胺破坏的肝细胞色素P-450的体内功能。
Biochem Biophys Res Commun. 1979 Jul 27;89(2):456-63. doi: 10.1016/0006-291x(79)90651-x.
7
Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital.致卟啉药物烯丙异丙基乙酰胺的生化效应。与苯巴比妥的比较研究。
Biochem J. 1973 Aug;134(4):859-68. doi: 10.1042/bj1340859.
8
Allylisopropylacetamide preferentially interacts with the phenobarbital-inducible form of rat hepatic microsomal P-450.
Biochem Pharmacol. 1976 Nov 1;25(21):2415-7. doi: 10.1016/0006-2952(76)90042-3.
9
[Changes in liver microsomal enzymes and the synthesis of delta-aminolevulinic acid in short-term exposure of rabbits to allylisopropylacetamide, hexachlorobenzene and phenobarbital].[家兔短期接触烯丙异丙基乙酰脲、六氯苯和苯巴比妥后肝微粒体酶的变化及δ-氨基乙酰丙酸的合成]
Eksp Med Morfol. 1982;21(3):110-5.
10
Destruction of cytochrome P-450 by 2-isopropyl-4-pentenamide and methyl 2-isopropyl-4-pentenoate: mass spectrometric characterization of prosthetic heme adducts and nonparticipation of epoxide metabolites.2-异丙基-4-戊烯酰胺和2-异丙基-4-戊烯酸甲酯对细胞色素P-450的破坏作用:辅基血红素加合物的质谱表征及环氧化物代谢产物未参与作用
Arch Biochem Biophys. 1979 Oct 15;197(2):524-33. doi: 10.1016/0003-9861(79)90276-5.

引用本文的文献

1
Effects of age, phenobarbital, beta-naphthoflavone and dexamethasone on rat hepatic heme oxygenase.年龄、苯巴比妥、β-萘黄酮及地塞米松对大鼠肝脏血红素加氧酶的影响
Arch Toxicol. 1994;68(1):32-6. doi: 10.1007/BF03035707.
2
Formation of cytochrome P-450 containing haem or cobalt-protoporphyrin in liver homogenates of rats treated with phenobarbital and allylisopropylacetamide.用苯巴比妥和烯丙异丙基乙酰胺处理的大鼠肝脏匀浆中含血红素或钴原卟啉的细胞色素P - 450的形成。
Biochem J. 1984 Sep 1;222(2):453-62. doi: 10.1042/bj2220453.
3
Differential haemin-mediated restoration of cytochrome P-450 N-demethylases after inactivation by allylisopropylacetamide.
烯丙基异丙基乙酰胺使细胞色素P-450 N-脱甲基酶失活后,血红素介导的差异性恢复
Biochem J. 1985 Apr 1;227(1):277-86. doi: 10.1042/bj2270277.
4
Cloning and characterization of cDNAs encoding 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible rabbit mRNAs for cytochrome P-450 isozymes 4 and 6.编码细胞色素P-450同工酶4和6的2,3,7,8-四氯二苯并对二恶英诱导的兔mRNA的cDNA的克隆与特性分析
Proc Natl Acad Sci U S A. 1985 Aug;82(16):5310-4. doi: 10.1073/pnas.82.16.5310.