The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking.
The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking.
复制标题
DOI：
10.1016/j.bbadis.2010.01.013
复制
发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Xie ZJ
中科院分区：
文献类型：
--
作者：
Liu J;Xie ZJ
Na/K-ATP酶是一种能量转换的离子泵。Na/K-ATP酶和其他P型ATP酶之间的主要区别是它能够结合一组称为强心类固醇（CTS）的化学物质。植物源性CTS如地高辛是治疗心脏疾病的重要药物，而哇巴因和海蟾毒配基（MBG）已被鉴定为一类新的内源性激素。近年来的研究表明，内源性CTS是肾脏Na+排泄和血压的重要调节因子。Na/K-ATP酶不仅是一个离子泵，而且是一个重要的受体，可以传导CTS对细胞内蛋白激酶和Ca 2+信号的配体样作用。值得注意的是，这些CTS引起的信号传导事件能够降低肾近端小管细胞中顶端NHE 3（Na/H交换器同种型3）和基底外侧Na/K-ATP酶的表面表达。这些结果表明，内源性CTS可能在生理条件下的肾小管Na+排泄的调节中发挥重要作用;相反，在受体水平（Na/K-ATP酶）或受体-效应器偶联的缺陷将降低肾近端肾小管细胞的Na+排泄能力，从而最终导致/导致盐敏感性高血压。
The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na+ excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect of CTS on intracellular protein kinases and Ca2+ signaling. Significantly, these CTS-provoked signaling events are capable of reducing the surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. These findings suggest that endogenous CTS may play an important role in regulation of tubular Na+ excretion under physiological conditions; conversely, a defect at either the receptor level (Na/K-ATPase) or receptor-effector coupling would reduce the ability of renal proximal tubular cells to excrete Na+, thus culminating/resulting in salt-sensitive hypertension.