小窝蛋白-3在PKC Eplison 介导缺血预适应心脏保护中的作用机制

项目名称： 小窝蛋白-3在PKC Eplison 介导缺血预适应心脏保护中的作用机制

项目编号： No.81200145

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 孙巍

作者单位： 吉林大学

项目金额： 24万元

中文摘要： 小窝蛋白-3（Cav-3）在缺血预适应动物模型中显示出心脏保护作用。Cav-3在细胞膜小窝中不仅起支架作用，还能调节信号蛋白的活化，是参与心肌保护作用关键蛋白的交汇点。蛋白激酶Ce(PKCe）在缺血预适应心脏保护中具有重要地位，前期工作证明：Cav-3 和PKCe共表达在细胞膜同一位置，通过调节腺苷A1受体促使PKCe转位进入细胞膜小窝，但PKCe进入小窝后与Cav-3是如何偶联的尚不清楚。已知Cav-3可与PKC信号通路中的KATP通道偶联并调节其活性，推测Cav-3在PKCe介导的缺血预适应中通过与KATP通道偶联发挥心脏保护作用。为了确认这种推测并研究其可能的分子机制，我们拟围绕Cav-3与KATP通道偶联，研究Cav-3与PKCe偶联、活化及转位的关系，利用计算机软件分析Cav-3与KATP通道的偶联活性位点，利用体内外模型揭示心肌缺血预适应中Cav-3与PKCe的偶联机制。

中文关键词： 蛋白激酶C；小窝蛋白-3；缺氧预适应；荧光共振能量转移；心肌细胞

英文摘要： Caveolin-3 (Cav-3) has been shown to play an important role in the cardioprotection of ischemic preconditioning. Cav-3 which is abundant in caveolae-provides a scaffold to organize, traffic, and regulate signaling molecules. Numerous signaling molecules involved in cardiac protection are known to exist within caveolae or interact directly with caveolin-3. PKC Eplison is one of the most important proteins involved in cardiac protection. Our previous study showed that Cav-3 is colocalized with PKCe in the cell membrane. Activation of adenosine A1 receptors induces translocation of PKCe to the membrane from the cytosol. But whether activated PKCe is binding with Cav-3 is still unknown. We confirmed that Cav-3 binding with endogenous octameric KATP channel in adult rat cardiac myocytes. We hypothesize that the association of KATP channel with Cav-3 plays the important role in PKC-mediated cardioprotection of ischemia preconditioning. The purpose of this study is to elucidate the role of Cav-3 binding with PKCe and to identify signaling mechanisms responsible for PKCe translocation and Cav-3. We will analyze the binding site of Cav-3 with KATP channel by computer software and we investigate that the signal components in cardiac protection coexist and function in the caveolae and that the interaction of signaling mole

英文关键词： PKC；Caveolin-3；hypoxia preconditioning；FRET；cardiomyocyte