GAPDH AND ITS PROTECTIVE ROLE IN ATHEROSCLEROSIS

GAPDH 及其在动脉粥样硬化中的保护作用

• 批准号: 7959753
• 负责人: Sergiy Sukhanov
• 金额: $ 7.66万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959753
• 关键词: Apoptosis; Arterial Fatty Streak; Atherosclerosis; Biology; Cardiovascular system; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA Damage; DNA Repair; Diet; Enzymes; Funding; Genome; Glyceraldehyde-3-Phosphate Dehydrogenases; Grant; In Vitro; Institution; Mentors; Oxidants; Oxidative Stress; Play; Production; Research; Research Personnel; Resources; Role; Smooth Muscle Myocytes; Source; Testing; Translating; United States National Institutes of Health; cell motility; in vivo

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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标志。甘油醛-3-磷酸脱氢酶（GAPDH）是一种多功能糖酵解酶，在能量生产中起着重要作用。GAPDH还保护细胞基因组的完整性，并且氧化应激修饰的GAPDH启动细胞凋亡。该项目的主要假设是，在SMC中恢复GAPDH水平将在体外对氧化剂诱导的细胞凋亡和细胞迁移的抑制以及在体内对饮食诱导的动脉粥样硬化具有保护作用。 我们将确定在SMC中有/无氧化剂的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进展相关，我们计划研究GAPDH是否在氧化剂诱导的SMC DNA损伤中起保护作用。我们还计划测试恢复动脉粥样硬化SMC中GAPDH水平是否会刺激细胞能量产生并导致动脉粥样硬化减少。