Potentiation and suppression of mouse liver cytochrome P-450 isozymes during the acute-phase response induced by bacterial endotoxin.

Potentiation and suppression of mouse liver cytochrome P-450 isozymes during the acute-phase response induced by bacterial endotoxin.
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细菌内毒素诱导的急性期反应期间小鼠肝细胞色素 P-450 同工酶的增强和抑制。

DOI:
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发表时间:
1988
期刊:
European Journal of Biochemistry
影响因子:
--
通讯作者:
C. Wolf
C. Wolf
中科院分区:
--
文献类型:
--
作者:
L. Stanley;D. Adams;R. Lindsay;R. Meehan;W. Liao;C. Wolf

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众所周知,感染和炎症会影响药物和致癌物的新陈代谢和处置。我们详细研究了细菌内毒素对P-450I、P-450IIB、P-450IIC和P-450III家族细胞色素P-450同工酶的结构性和诱导性表达及活性的影响。一般来说,高剂量的高内毒素会导致P-450同工酶及其相关活性受到非常显着的抑制。然而,这种影响是不同的,某些同工酶的表达仅略有减少,而其他同工酶的表达被抑制到几乎检测不到的水平。低剂量内毒素对细胞色素P-450的表达也有不同程度的影响。特别令人感兴趣的是,3-甲基胆蒽和苯巴比妥的诱导作用都有非常显著的增强。在3-甲基胆蒽的情况下,通过同时给予内毒素,活性诱导增加了10倍至24倍。在这方面,有趣的是,3-甲基胆菲是一种有效的多种急性时相蛋白的诱导剂,包括金属硫蛋白、血清淀粉样蛋白A、纤维蛋白原和血凝素。这些数据表明,内毒素,从而细菌感染和炎症,可以对细胞色素-P-450单加氧酶系统的成分产生深刻而不同的影响,从而导致对药物、化学毒素和致癌物影响的敏感性发生重大变化。
Infection and inflammation are known to affect the metabolism and disposition of drugs and carcinogens. We report a detailed study of the effects of bacterial endotoxin on the constitutive and inducible expression and activities of cytochrome P-450 isozymes from families P-450I, P-450IIB, P-450IIC and P-450III. In general high doses of high endotoxin caused very marked suppression of P-450 isozymes and associated activities. However, this effect was differential, the expression of certain isozymes being only slightly reduced whereas others were suppressed to almost undetectable levels. Low doses of endotoxin also gave differential effects on cytochrome P-450 expression. Of particular interest was the very marked potentiation of the inductive effect of both 3-methylcholanthrene and phenobarbital. In the case of 3-methylcholanthrene the 10-fold induction of activity was increased to 24-fold by concomitant endotoxin administration. In this regard it was interesting that 3-methylcholanthrene was an effective inducer of a wide variety of acute-phase proteins including metallothionein, serum amyloid A, fibrinogen and hemopexin. These data show that endotoxin, and therefore bacterial infection and inflammation, can have profound and differential effects on components of the cytochrome-P-450 monooxygenase system which could result in significant changes in susceptibility to the effects of drugs, chemical toxins and carcinogens.
DOI: --
发表时间: 1986
期刊: The Journal of biological chemistry
影响因子: --
作者:
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DOI: --
发表时间: 1985
影响因子: 3.6
作者:
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DOI: 10.1021/bi00289a035
发表时间: 1983
期刊: Biochemistry
影响因子: 2.9
作者:
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DOI: 10.1016/0003-9861(86)90490-x
发表时间: 1986
影响因子: 3.9
作者:
Mathis,JM;Prough,RA;Hines,RN;Bresnick,E;Simpson,ER
通讯作者: Simpson,ER
四种大鼠肝微粒体细胞色素 P-450 的 NH2 末端序列分析。
DOI: 10.1016/0003-9861(84)90202-9
发表时间: 1984
影响因子: 3.9
作者:
Haniu,M;Ryan,DE;Iida,S;Lieber,CS;Levin,W;Shively,JE
通讯作者: Shively,JE