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

为探讨心肌型肌浆网钙ATP酶（SERCA 2a）的调节机制，建立了大鼠心肌细胞原代培养模型，并通过电刺激观察了心肌细胞的物理特性和钙瞬变。研究结果如下。我们研究了丙烯醛，吸烟的加合物，对心肌细胞的影响。结果表明，丙烯醛降低了心肌细胞的功能，并最终诱导了心肌细胞凋亡。丙烯醛还诱导人脐静脉内皮细胞（HUVEC）发生细胞凋亡，这可能与吸烟相关的动脉粥样硬化有关。研究了心肌兰尼碱受体的调节机制，该受体也是心肌的有效调节剂。我们发现早老素-2作为心脏ryanodine受体的调节剂。结果表明，早老素-2以钙依赖性方式与心肌ryanodine受体结合，控制心脏功能。此外，我们发现，受磷蛋白（PLN），SERCA 2a的内源性调节剂，是O-G1 cNAc酰化和PLN的抑制功能是由O-G1 cNAc酰化调节。

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.