The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)
The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)
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DOI：
10.1139/cjpp-2014-0463
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发表时间：
2015-10-01
影响因子：
2.1
通讯作者：
Duhamel, Todd A.
中科院分区：
文献类型：
--
作者：
Stammers, Andrew N.;Susser, Shanel E.;Duhamel, Todd A.
肌浆网钙atp酶（SERCA）负责在肌肉收缩后将钙（Ca2+）从细胞质转运到肌浆网（SR）的管腔。SERCA的Ca2+隔离活性促进心肌和骨骼肌的肌肉松弛。SERCA在不同组织中表达的亚型超过10种。SERCA2a是在心脏组织中表达的主要亚型，而SERCA1a是在快速收缩骨骼肌中表达的主要亚型。SERCA的Ca2+螯合活性在蛋白含量水平上受到调控，并进一步受到内源蛋白磷蛋白（phospholamban， PLN）和肌磷脂（sarcolpin， SLN）的修饰。此外，一些新的机制，包括翻译后修饰和microRNAs （miRNAs）正在成为Ca2+运输活性的整体调节剂。这些调节机制具有临床相关性，因为SERCA功能失调与包括心力衰竭在内的几种疾病的病理状态有关。目前，一些临床试验正在进行中，利用新的治疗方法来恢复人类SERCA2a的活性。本综述的目的是研究SERCA泵的调节机制，特别强调运动对预防与SERCA功能受损相关的病理状况的影响。
The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca2+) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca2+ sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca2+ sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca2+ transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.