可溶性耐药相关钙结合蛋白

可溶性耐药相关钙结合蛋白(sorcin)是一个21.6 kD的胞浆蛋白，具有典型的EF手臂(EF-hand)钙结合位点, 广泛存在于多种组织中，在心肌细胞中含量最丰富.Sorcin可与肌浆网钙离子通道RyR相互作用影响心肌细胞兴奋——收缩偶联.另一方面，sorcin在肿瘤耐药细胞中大量表达，它可以与细胞中钙离子结合，引起细胞内游离钙离子浓度下降，然后导致钙离子所介导的磷酸酶活性降低，使得具有排药功能的P-gp糖蛋白磷酸化水平下降，最终导致耐药.一旦明确引发和维持细胞耐药的作用机制，就可为克服肿瘤耐药提供新的靶点.同时随着RyR活性抑制作用研究的深入，有望通过sorcin转基因技术治疗心力衰竭.本文主要对sorcin的结构特点和生物学特性进行综述，并初步分析其耐药机制.

Soluble Resistance-related Calcium Binding Protein

Soluble resistance-related calcium binding protein (sorcin), a 21.6 kD calcium-binding protein that has the typical "EF-hand" calcium-binding recognition site. Sorcin is widely distributed in many tissues, especially in cardiac myocytes. Sorcin is associated with the cardiac ryanodine receptor (RyR) during EC coupling of myocardial cells. Sorcin is also overexpressed in tumor resistant cells. It can bind Ca~ 2 , decreasing the concentration of Ca~ 2 transiently and depressing the activity of phosphatase, which in turn reduces the phosphorylation level of P-glycoprotein, resulting in drug resistance of cells. Once the mechanism of solicitation and maintenance of drug resistance is clarified, a new trigger is offered for overcoming the drug resistance of tumor. In the meantime, with future study on the inhibition of RyR activity, it is quite promising that heart failure can be treated with transgene-technology of sorcin. This review summarizes the structure and characteristics of sorcin and analyses its drug resistance mechanism.