Early aldosterone action: toward filling the gap between transcription and transport.

Early aldosterone action: toward filling the gap between transcription and transport.
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早期醛固酮作用:填补转录和运输之间的空白。

DOI:
10.1152/ajprenal.1999.277.3.f319
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发表时间:
1999
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
F. Verrey
F. Verrey
中科院分区:
--
文献类型:
--
作者:
F. Verrey

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盐皮质激素醛固酮在 20 至 60 分钟的滞后期后,首先激活预先存在的通道(上皮钠通道,ENaC)和泵(Na-K​​-ATPase),然后增加细胞的整体转运能力,从而刺激目标上皮细胞的跨细胞 Na+ 重吸收。这些早期调节和晚期合成代谢型作用均取决于激素激活的盐皮质激素和/或糖皮质激素受体(MR 和/或 GR)所施加的转录调节。从醛固酮作用的转录侧开始,最近的研究已确定小 G 蛋白 K-Ras2 和激酶 sgk 是第一个可能调节 Na+ 转运的早期醛固酮诱导基因产物。在 Na+ 转运效应子水平上,积累了大量关于 ENaC 和 Na-K-ATPase 结构功能关系和调节的知识。然而,将醛固酮转录作用与这些 Na+ 转运蛋白联系起来的调控途径在很大程度上仍然未知。现有数据表明醛固酮的早期调节作用是多效性的,类似于晚期合成代谢型作用。早期Na+转运刺激将​​通过属于调控网络的基因产物的快速诱导来介导,该调控网络整合了不同途径的输入并最终控制Na+转运机制的功能。
The mineralocorticoid hormone aldosterone stimulates transcellular Na+ reabsorption across target epithelia after a lag period of 20 to 60 min by first activating preexisting channels (epithelial sodium channels, ENaC) and pumps (Na-K-ATPase) and, subsequently, increasing the overall transport capacity of the cells. Both these early regulatory and late anabolic-type actions depend on the transcriptional regulation exerted by hormone-activated mineralocorticoid and/or glucocorticoid receptors (MR and/or GR). Starting at the transcriptional side of the aldosterone action, recent studies have identified the small G protein K-Ras2 and the kinase sgk as the first early aldosterone-induced gene products potentially regulating Na+ transport. At the level of the Na+ transport effectors, much knowledge about ENaC and Na-K-ATPase structure-function relationship and regulation has accumulated. However, the regulatory pathway(s) that link the transcriptional action of aldosterone to these Na+ transport proteins is still to a large extent unknown. The available data suggest that the early regulatory action of aldosterone is pleiotropic, similarly to the late anabolic-type action. The early Na+ transport stimulation would be mediated by the rapid induction of gene products belonging to the regulatory network that integrates the inputs of diverse pathways and finally controls the function of the Na+ transport machinery.
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