PLN蛋白复合物调控心脏泵功能研究概论及前景展望

Modulation of PLN Complex on Cardiac Pump Function and Perspectives

肌浆网(SR)钙转运功能障碍为目前公认的人和动物实验性心力衰竭的主要病理特征,SR钙转运受多个蛋白复合物的调控,包括:蛋白激酶及蛋白磷酸化酶以及一些与之相互结合的蛋白和调控亚基,这些蛋白共同作用精细调节肌浆网的钙转运。其中,SR钙摄入受SR Ca-ATPase(SERCA2a)及其磷酸化调控蛋白phospholamban(PLN)的调控,近年来研究显示:除SERCA2a和PLN之外机体内还存在其它与PLN相关的调控SR钙转运的因子,主要包括:蛋白磷酸化酶1抑制因子、热休克蛋白20(HSP20)和HS相关蛋白X-1(HAX-1)等,这些蛋白质与PLN之间存在直接或间接的相互作用通过蛋白复合物的形式精细调控SR的钙摄入、贮存和释放。值得一提的是,PLN/SERCA2a及其相关复合物不仅可调控心肌收缩功能,还可调控动物生存率及心肌重塑;人体研究发现上述SR相关蛋白的基因突变及活性改变也可导致心肌收缩功能抑制以及心室重塑,预期这些遗传学方面的改变可作为心脏病理生理的预后和诊断标志物。

The major cause of human and experimental heart failure is related to the deregulated sarcoplasmic reticulum( SR) calcium cycling,controlled by several protein complexes. Those complexes,including protein kinase,protein phosphatase and some interacting proteins or subunits,work together to maintain normal cytosolic calcium homeostasis.Among them,SR calcium transport is regulated by SR calcium ATPase and the phosphorylated protein: phospholamban( PLN). Recently,some other proteins,such as: protein phosphatase 1 inhibitor 1,heat shock protein 20( HSP20) and HS-associated protein X-1( HAX-1) have been reported to play an important role in SR calcium handing as well as cardiac function. This review will focus on the recent findings in these PLN interacting complex and their contribution in cardiac pump function as well as the potential clinical application.