Molecular mechanism of the regulating factors for sarcoplasmic reticulum Ca-ATPase

为探讨在心功能中起重要作用的心型sarco（endo）质网ca - atp酶（SERCA2a）的调控机制，建立大鼠成年心肌细胞原代培养，测定不同处理后心肌细胞电痉挛的物理形态和钙瞬态。研究结果如下：我们研究了丙烯醛（吸烟的一种加合物）对心肌细胞的影响。结果，丙烯醛降低心肌细胞功能，最终诱导心肌细胞凋亡。丙烯醛诱导人脐静脉内皮细胞（HUVEC）凋亡，可能与吸烟相关的动脉粥样硬化有关。本文探讨了心肌的强效调节剂——红胺受体的调节机制。我们发现present - alin-2是心脏ryanodine受体的调节因子。研究表明，present - alin-2以钙依赖的方式与心脏ryanodine受体结合并控制心功能。此外，我们发现SERCA2a的内源性调节因子phospholamban （PLN）被o - g1cn酰化，并且PLN的抑制功能受到o - g1cn酰化的调节。

To examine the regulatory mechanism of cardiac type sarco(endo)plasmic reticulum Ca-ATPase(SERCA2a), which plays an important role in cardiac function, the primary cell culture of rat adult cardiomyocytes was espablished, and the physical profile and calcium transient of cardiomyocytes by electrical twitches were measured after various treatments. The research results are as follows. We investigated the effect of acrolein, an adduct of cigarette smoking, on cardiomyocytes. As a result, acrolein reduced the fuction of cardiomyocytes and eventually induced apoptosis. The apoptosis by acrolein was also induced in human umbilical vein endothelial cells (HUVEC), which might be involved in atherosclerosis related to cigarette smoking. The regulatory mechanism of cardiac ryanodine receptor, which is also the potent regulator of cardiac muscle, was examined. We found presenalin-2 as a regulator of cardiac ryanodine receptor. It was shown that presenalin-2 bound to cardiac ryanodine receptor in a calcium dependent manner and controlled the cardiac function. Furthermore, we revealed that phospholamban (PLN), an endogenous regulator of SERCA2a, was O-G1cNAcylated and the inhibitory function of PLN was regulated by the O-G1cNAcylation.