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肌型肌浆网钙-三磷酸腺苷酶(SERCA2a)的调节机制，建立了成年大鼠心肌细胞原代培养模型，测定了不同处理后心肌细胞的形态及电抽动引起的心肌细胞钙瞬变。研究结果如下。我们研究了吸烟的加合物丙烯醛对心肌细胞的影响。结果，丙烯醛降低了心肌细胞的功能，最终诱导了细胞凋亡。丙烯醛还可诱导人脐静脉内皮细胞(HUVEC)发生凋亡，这可能与吸烟引起的动脉粥样硬化有关。研究了心肌兰尼定受体的调节机制，该受体也是心肌的有力调节剂。我们发现前脑啡肽-2是心脏兰尼定受体的调节剂。结果表明，早老素-2以钙依赖的方式与心脏兰尼定受体结合，控制心功能。此外，我们还发现SERCA2a的内源性调节因子磷脂酰化蛋白(PLN)是O-G1cN酰化的，其抑制功能受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.