GAPDH AND ITS PROTECTIVE ROLE IN ATHEROSCLEROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 能量产生不足、DNA修复受损和平滑肌细胞(SMC)凋亡是晚期动脉粥样硬化斑块的特征。甘油醛-3-磷酸脱氢酶(GAPDH)是一种多功能糖酵解酶，在能量生产中起重要作用。GAPDH还保护细胞基因组的完整性，氧化应激修饰的GAPDH启动细胞凋亡。该项目的主要假设是，在体外，恢复SMC中GAPDH的水平将保护细胞免受氧化剂诱导的细胞凋亡和细胞迁移的抑制，并在体内防止饮食诱导的动脉粥样硬化。我们将确定在有或没有氧化剂的情况下，对SMC中GAPDH水平的操纵是否会转化为细胞迁移和凋亡的适当变化。由于进行性DNA损伤与动脉粥样硬化的进展有关，我们计划研究GAPDH在氧化剂诱导的SMC DNA损伤中是否起到保护作用。我们还计划测试在动脉粥样硬化的SMC中恢复GAPDH水平是否会刺激细胞能量产生并导致动脉粥样硬化的减少。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Insufficient energy production, impaired DNA repairing and smooth muscle cell (SMC) apoptosis are hallmarks of advanced atherosclerotic plaque. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional glycolytic enzyme that plays an important role in energy production. GAPDH also protects the cell genome integrity and oxidative stress-modified GAPDH initiates the cell apoptosis. The major hypothesis of this project that restoring GAPDH levels in SMC would be protective against oxidant-induced apoptosis and suppression of cell migration in vitro and against diet-induced atherosclerosis in vivo. We will determine if manipulation of GAPDH levels in SMC with/without oxidant would be translated into adequate changes in cell migration and apoptosis. Since progressive DNA damage is associated with atherosclerosis progression, we plan to study if GAPDH plays a protective role in oxidant-induced DNA damage in SMC. We also plan to test if restoring GAPDH levels in atherosclerotic SMC would stimulate cell energy production and leads to a reduction in atherosclerosis.