Regulation of cytochrome P-450c by glucocorticoids and polycyclic aromatic hydrocarbons in cultured fetal rat hepatocytes.

Regulation of cytochrome P-450c by glucocorticoids and polycyclic aromatic hydrocarbons in cultured fetal rat hepatocytes.
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糖皮质激素和多环芳烃对培养胎鼠肝细胞中细胞色素 P-450c 的调节。

DOI:
10.1016/0003-9861(86)90490-x
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发表时间:
1986
影响因子:
3.9
通讯作者:
Simpson,ER
Simpson,ER
中科院分区:
生物学3区
文献类型:
--
作者:
Mathis,JM;Prough,RA;Hines,RN;Bresnick,E;Simpson,ER

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在原代单层培养的胎鼠肝细胞中,研究了多环芳烃和糖皮质激素对细胞色素p -450c(多环芳烃诱导的主要同工酶)合成的调控作用。用1,2-苯并蒽处理培养的肝细胞导致7-乙氧基香豆素去乙基酶活性增加50倍。通过免疫电泳分析,细胞中p -450的水平以时间依赖性的方式增加。当培养基中加入1 μmdexamethasone时,BA的诱导作用增强约1.6 ~ 2.3倍。然而,单独使用地塞米松对p -450c的诱导作用很小或没有影响。通过免疫分离用[35S]蛋氨酸放射标记的细胞总蛋白和分离的mRNA体外翻译过程中形成的蛋白产物,检测p -450c的合成速率。此外,通过对培养细胞中提取的RNA进行Northern blot分析,确定细胞色素p -450c特异性mRNA的数量。合成速率和mRNA水平的变化与酶活性的变化一致。在1,2-苯并蒽存在的情况下,使p -450含量增加一半所需的地塞米松浓度在10−8 ~ 10−7m之间。综上所述,糖皮质激素与多环芳烃协同作用,提高胎鼠肝脏中p -450的表达水平,这种作用可能是由经典的II型糖皮质激素受体介导的。
The actions of polycyclic aromatic hydrocarbons and glucocorticoids to regulate the synthesis of cytochromeP-450c(the major isozyme induced by polycyclic aromatic hydrocarbons) were investigated in fetal rat hepatocytes maintained in primary monolayer culture. Treatment of hepatocytes in culture with 1,2-benzanthracene resulted in a 50-fold increase in 7-ethoxycoumarinO-deethylase activity. The level ofP-450cincreased in the cells in a time-dependent fashion as determined by immunoelectrophoretic analysis. The inductive effect of BA was potentiated approximately 1.6- to 2.3-fold when 1 μmdexamethasone was included in the culture medium. However, dexamethasone alone had little or no effect on the induction ofP-450c. The rate of synthesis ofP-450cwas examined by immunoisolation of the specific isozyme from total cellular proteins radiolabeled with [35S]methionine and from the protein products formed duringin vitrotranslation of the isolated mRNA. In addition, the amount of mRNA specific for cytochromeP-450cwas determined by Northern blot analysis of RNA extracted from cultured cells. The changes in the rates of synthesis and mRNA levels were found to parallel the changes in enzyme activity. The concentration of dexamethasone required to cause a half-maximal increase inP-450ccontent in the presence of 1,2-benzanthracene was between 10−8and 10−7m. It is concluded that glucocorticoids act synergistically with polycyclic aromatic hydrocarbons to increase the levels ofP-450cexpressed in the fetal rat liver, and that this action is likely mediated by the classical type II glucocorticoid receptor.
3-甲基胆蒽诱导细胞色素 P-450c 基因的表达。
DOI: --
发表时间: 1985
影响因子: 3.9
作者:
R. Foldes;R. Hines;K. Ho;M. Shen;K. Nagel;E. Bresnick
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胎鼠肝切片中尿素合成的控制。
DOI: 10.1159/000241496
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期刊: Biology of the neonate
影响因子: --
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DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
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细胞色素 P-450 的多种形式以及分子生物学和进化的重要性。
DOI: 10.1016/0006-2952(82)90523-8
发表时间: 1982
影响因子: 5.8
作者:
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类固醇和大鼠组织的成熟。
DOI: 10.1016/0022-4731(75)90045-x
发表时间: 1975
期刊: Journal of steroid biochemistry
影响因子: --
作者:
O. Greengard
通讯作者: O. Greengard