心肌细胞凋亡是多种心脏疾病最终不可逆转归为心力衰竭的根本原因。目前，特定蛋白磷酸化修饰在心肌细胞凋亡中的作用日益引起关注。我们前期研究发现，兼职功能蛋白α-enolase是调控心肌细胞凋亡的重要因子，在凋亡过程中，α-enolase的亚细胞定位和生物功能历经复杂的动态变化，提示其在期间可能发生了翻译后修饰状态的改变。本课题将在此基础上，采用亲和层析和免疫印迹技术研究凋亡诱导因子多柔比星作用下，心肌α-enolase磷酸化水平的改变；并采用LC/MS鉴定发生磷酸化修饰变化的氨基酸残基；进一步利用DNA突变与基因过表达技术，在细胞和动物水平深入研究α-enolase特定位点磷酸化修饰对心肌细胞凋亡的调控作用，并探讨相关分子机制。本研究将发现α-enolase亚细胞定位与功能调节的结构基础，也为α-enolase作为心力衰竭治疗靶点的研究和开发提供科学依据。

Cardiomyocyte apoptosis is a common pathological alteration in heart disease which results in systolic dysfunction and eventually heart failure. Recently, the phosphorylation of specific proteins in controlling cardiomyocyte apoptosis has attracted considerable attentions. According to our previous study, α-enolase plays an important role in cardiomyocyte apoptosis, which suffers complex changes in its subcellular distribution and biological function. In the present project, we are going to study the involvement of α-enolase phosphorylation in cardiomyocyte apoptosis as well as the underlying mechanism. In doxorubicin-treated cardiomyocytes and rat hearts, the phosphorylated amino acid residues of α-enolase are going to be analyzed by affinity chromatography and LC/MS. Then the role of the phosphorylated residues in cardiomyocyte apoptosis is going to be investigated by technologies including DNA mutation, gene clone and overexpression at a cellular level and in animals. The underlying mechanism is also going to be studied. Our findings will explain the molecular basis of α-enolase’s multi-functions and its cellular compartmentalization, and raise the possibility that the protein may be utilized as a target to prevent cardiomyocyte apoptosis and heart failure.