Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets.
Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets.
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DOI：
10.1124/pr.108.000711
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发表时间：
2009-03
影响因子：
21.1
通讯作者：
Fedorova OV
中科院分区：
文献类型：
--
作者：
Bagrov AY;Shapiro JI;Fedorova OV
内源性强心性类固醇(CTS)，又称洋地黄样因子，近半个世纪以来一直被认为在健康和疾病中发挥着重要作用。最近的发现，包括在人类中特异性地鉴定内源性Cardenolide(内源性哇巴因)和Bufadienolide(Marinobufagenin)CTS，以及描述了CTS通过Na+/K+-ATPase发出信号的另一种机制，大大增加了对这一领域的兴趣。虽然CTS最初被认为在调节肾脏钠转运和动脉压方面很重要，但最近的研究表明，这些激素参与了细胞生长、分化、凋亡和纤维化的调节，免疫和碳水化合物代谢的调节，以及各种中枢神经功能甚至行为的控制。本文就CTS与其他调节系统之间的生理相互作用作一综述，这些系统在高血压、子痫前期、终末期肾病、充血性心力衰竭和糖尿病的病理生理学中可能起重要作用。根据我们对CTS的调节以及这些激素增加的分子机制的日益了解，我们还讨论了潜在的治疗策略。
Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, have been postulated to play important roles in health and disease for nearly half a century. Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by which CTS can signal through the Na+/K+-ATPase, have increased the interest in this field substantially. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the regulation of cell growth, differentiation, apoptosis, and fibrosis, the modulation of immunity and of carbohydrate metabolism, and the control of various central nervous functions and even behavior. This review focuses on the physiological interactions between CTS and other regulatory systems that may be important in the pathophysiology of essential hypertension, preeclampsia, end-stage renal disease, congestive heart failure, and diabetes mellitus. Based on our increasing understanding of the regulation of CTS as well as the molecular mechanisms of these hormone increases, we also discuss potential therapeutic strategies.
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