EVIDENCE FOR THE LIGAND-INDEPENDENT ACTIVATION OF THE AH RECEPTOR
EVIDENCE FOR THE LIGAND-INDEPENDENT ACTIVATION OF THE AH RECEPTOR
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DOI：
10.1006/bbrc.1995.1526
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发表时间：
1995-04-17
影响因子：
3.1
通讯作者：
HOOGENBOOM, L
中科院分区：
文献类型：
--
作者：
LESCA, P;PERYT, B;HOOGENBOOM, L
苯并咪唑衍生物是兔和人肝细胞中CYP 1A 1的强效诱导剂，但显然不结合AH受体。为了解决这一矛盾的行为，研究一直关注的问题是，是否有一种替代的配体非依赖性机制可以解释AH受体的激活。从实验中培养的兔肝细胞，我们表明，苯并咪唑结合早期和短暂的未知蛋白质。此外，它们能够以时间和剂量依赖性方式消耗AHR。相比之下，苯并咪唑不能诱导小鼠hepa-1细胞中的CYP 1A 1 mRNA，并从这些细胞中消耗高亲和力AHR形式。总之，这些数据表明，一个信号转导途径，类似于参与类固醇受体的配体非依赖性激活，只能激活低亲和力形式的AHR作为那些存在于兔和人细胞。(C)北京：科学出版社. Inc.
Benzimidazole derivatives are potent inducers of CYP1A1 in rabbit and human hepatocytes, but apparently do not bind the AH receptor. To resolve this paradoxical behaviour, studies have been concerned with the question of whether an alternative ligand-independent mechanism could explain the activation of the AH receptor. From experiments in cultured rabbit hepatocytes we show that benzimidazoles bind early and transiently to an unknown protein. Moreover, they are able to deplete the AHR in a time- and dose-dependent manner. In contrast, benzimidazoles are unable to induce CYP1A1 mRNA in mouse hepa-1 cells and to deplete the high-affinity AHR form from these cells. Taken together these data suggest that a signal transduction pathway, similar to that involved in the ligand-independent activation of steroid receptors, could only activate the low-affinity forms of AHR as those existing in rabbit and human cells. (C) 1995 Academic Press. Inc.