Rodriguez P, Kranias E G
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, OH, USA.
Arch Mal Coeur Vaiss. 2005 Dec;98(12):1239-43.
Our knowledge and understanding of the normal and diseased heart has advanced significantly over the past decade. Evidence indicates that several signaling pathways involved in the induction of cardiac disease and heart failure are associated with abnormal calcium handling by the sarcoplasmic reticulum proteins: calcium-ATPase pump and phospholamban. Indeed, the failing heart is characterized by impaired removal of cytosolic calcium, reduced loading of the cardiac sarcoplasmic reticulum, and defective calcium release, culminating in impairment of cardiac diastolic and systolic function. This review summarizes studies which highlight the key role of the sarcoplasmic reticulum proteins, calcium-ATPase pump and phospholamban, in the regulation of cardiac function; the significance of the phospholamban interaction with the calcium-ATPase pump through transgenic animal models; the recent findings of the inhbitor-1 of protein phosphatase-1 as a new potential therapeutic agent in heart failure; and finally, the discoveries of human phospholamban mutations leading to disease states.
在过去十年中，我们对正常心脏和患病心脏的认识与理解有了显著进展。有证据表明，参与诱发心脏病和心力衰竭的几种信号通路与肌浆网蛋白（钙 - ATP酶泵和受磷蛋白）对钙的异常处理有关。事实上，衰竭心脏的特征是胞质钙清除受损、心肌肌浆网钙负荷减少以及钙释放缺陷，最终导致心脏舒张和收缩功能受损。这篇综述总结了一些研究，这些研究突出了肌浆网蛋白、钙 - ATP酶泵和受磷蛋白在心脏功能调节中的关键作用；通过转基因动物模型研究受磷蛋白与钙 - ATP酶泵相互作用的意义；蛋白磷酸酶 - 1抑制剂 - 1作为心力衰竭新潜在治疗药物的最新发现；以及最后，导致疾病状态的人类受磷蛋白突变的发现。
