线粒体铁硫蛋白-CaSR-Abl调节通路在缺氧性肺动脉高压发生机制中的作用

项目名称： 线粒体铁硫蛋白-CaSR-Abl调节通路在缺氧性肺动脉高压发生机制中的作用

项目编号： No.81470252

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 汪涛

作者单位： 华中科技大学

项目金额： 70万元

中文摘要： 缺氧性肺动脉高压（PH）的发生机制还不完全清楚。线粒体铁硫蛋白（RISP）感受缺氧，引起活性氧生成增加，进而导致细胞质内游离钙离子浓度（ [Ca2+]i）升高，介导缺氧肺血管收缩。Abl (Abelson tyrosine kinase)是一个非常重要的蛋白激酶。研究显示，Abl能促进平滑肌的收缩和增殖。我们的预实验发现Abl表达的下调能够抑制RISP的表达。缺氧时他们之间的联系尚未见报道。此外，课题组先前的研究发现细胞外钙敏感受体（CaSR）通过对[Ca2+]i的调节在缺氧性肺动脉收缩中发挥重要作用。那么RISP做为活性氧产生的关键因素，其与CaSR之间的相互作用尚未见报道。同时，研究显示[Ca2+]i同样可以调节Abl的功能。所以本课题基于先前的研究和预实验，研究RISP-CaSR-Abl通路在人体缺氧性肺动脉高压中的调控作用。旨在原有基础上，进一步探索缺氧性肺动脉高压的机制。

中文关键词： 缺氧性肺动脉高压；钙离子；线粒体铁硫蛋白；活性氧；Abl蛋白激酶

英文摘要： The mechanism of hypoxic pulmonary artery hypertension(PH) has still not been fully elucidated. Mitochondrial rieske iron-sulfur protein(RISP) may serve as an essential, primary molecule that mediates the hypoxic ROS generation. However, the mechanism that regulate the function of RISP have not completely understood. Abl (Abelson tyrosine kinase, c-Abl (Abelson tyrosine kinase, Abl) is an important protein kinase. Some studies have shown that c-Abl may induce smooth muscle contraction and proliferation. Our previous studies have shown that Abl-knockdown decrease the expression of RISP.The interaction of RISP with Abl has not been reported.In addition ,our previous studies have shown that extracellular calcium-sensing receptor (CaSR) is critical in hypoxic pulmonary vasoconstriction.mitochondria play an important role in HPV. Cytosolic Ca2+ concentration ([Ca2+]i) play an important role in many physiological conditions. How does the passageway of mitochondrial RISP-CaSR-Abl regulate hypoxic pulmonary artery hypertension? At present , correlational research have not been reported. The objective of this project is to study the effect and the mechanism of mitochondrial RISP-CaSR-Abl on the human hypoxic pulmonary artery hypertension. The study will provide new direction and measures for hypoxic pulmonary hypertension investigation.

英文关键词： hypoxic pulmonary artery hypertension;calcium;Rieske iron sulfur protein;Reactive oxygen species;Abelson tyrosine kinase