14-3-3η蛋白对BCL-2线粒体亚定位的分子导向作用及其抑制EPCs凋亡效应

Endothelial progenitor cells(EPCs) are widely involved in the angiogenesis process as the precursor cells of vascular endothelial cells. Our previous research showed that both 14-3-3 and Bcl-2 proteins have influence on the apoptosis of EPCs, and the mechanism may related to the closure of mPTP on mitochondrial membrane. We assume that its endogenous protective effects are not isolated phenomenon, but rather the result of their interaction. This program will build transgenic EPCs cell model and 14-3-3η gene knockout animal model for the purpose of investigating the molecular orientation effect of 14-3-3η on Bcl-2 during EPCs’ apoptosis process dynamically, discussing the effects of subcellar localization of mitochondrial membrane of 14-3-3ηBcl-2 complex on mitochondrial metabolism, and finally clarifying the mechanism of 14-3-3η protein’s inhibite on the apoptosis of EPCs to lay the foundation for the development of targeted drugs that based on inhibiting the apoptosis of EPCs for cardiovascular disease.

内皮祖细胞(EPCs)是血管内皮细胞前体细胞，广泛参与了心血管疾病血管新生过程。我们前期研究发现，14-3-3η蛋白和Bcl-2蛋白均能影响EPCs凋亡过程，机制与线粒体膜上mPTP关闭有关。我们假设其内源性保护作用并不是“孤立”的，而是其间交互作用的结果。本项目建立转基因EPCs细胞模型和14-3-3η基因敲除动物模型，动态研究EPCs凋亡过程14-3-3η对Bcl-2的分子导向作用，探讨14-3-3η-Bcl-2复合体的线粒体膜亚定位对线粒体代谢的影响，在代谢和分子水平阐明14-3-3η蛋白抑制EPCs凋亡的机制，为研发基于抑制EPCs凋亡的靶向心血管疾病康复药物奠定基础。

内皮祖细胞(EPCs)是血管内皮细胞前体细胞，广泛参与了心血管疾病血管新生过程。我们前期研究发现，14-3-3η蛋白和Bcl-2蛋白均能影响EPCs凋亡过程，机制与线粒体膜上mPTP关闭有关。我们假设其内源性保护作用并不是“孤立”的，而是其间交互作用的结果。本项目建立转基因EPCs细胞模型，动态研究EPCs凋亡过程14-3-3η对Bcl-2的分子导向作用，探讨14-3-3η-Bcl-2复合体的线粒体膜亚定位对线粒体代谢的影响，在代谢和分子水平阐明14-3-3η蛋白抑制EPCs凋亡的机制，为研发基于抑制EPCs凋亡的靶向心血管疾病康复药物奠定基础。