REDOX STATUS AND ANTIOXIDANTS IN PLATELET FUNCTION

血小板功能中的氧化还原状态和抗氧化剂

• 批准号: 2798631
• 负责人: JANE E Freedman
• 金额: $ 8.3万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2798631
• 关键词: antioxidants; ascorbate; enzyme activity; flow cytometry; glutathione; glutathione peroxidase; intracellular transport; laboratory rat; nitric oxide synthase; nitrosourea; nutrition related tag; oxidation reduction reaction; oxidative stress; platelet aggregation; protein kinase C; selenium; tocopherols; urate

DESCRIPTION (Adapted from the applicant's abstract) Epidemiological studies have shown that antioxidants play a role in the prevention of cardiovascular disease in humans and that dietary antioxidant consumption is inversely associated with the development of coronary artery disease. The precise mechanisms that underlie these observations, however, are not clear. While the beneficial effects of antioxidants have been attributed to the prevention of oxidative modification of low-density lipoprotein (LDL) and the inhibition of atherogenesis, other factors may also be important. Preliminary data presented in this application suggests that platelet function is dependent upon the balance between oxidative stress and antioxidant protection. In the first two years of this proposal, the applicant will study antioxidant biochemistry and free radical chemistry under the direction of Dr. Balz Frei, Ph.D., an established investigator in this field. The applicant will participate in successful research already in progress in Dr. Frei's laboratory and begin to specifically address the first aim of the proposal; namely, the effect of cytosolic antioxidant status on platelet function and the mechanisms responsible for any observed effects. In the latter three years the applicant will begin a period of independent investigation further examining the biochemical and molecular effects of antioxidants on platelet function with the sponsor of this proposal, Dr. Joseph Loscalzo, M.D., Ph.D. During this period, the applicant will: 1) characterize the role of membrane antioxidant status in modulating platelet function and 2) determine the in vivo relevance of these findings by studying an antioxidant-depleted or - supplemented animal model. The work contained in this proposal will provide new insights into the mechanism(s) by which antioxidants provide benefit for patients with vascular disease. The applicant's ultimate goal is to pursue the preliminary data presented in this application and develop an independent research program examining the interaction between cellular redox status, antioxidants, and vascular homeostasis.

描述 （摘自申请人摘要）流行病学研究表明， 抗氧化剂在预防心血管疾病中发挥作用， 人类和饮食中的抗氧化剂消耗量与 冠状动脉疾病的发展。 的精确机制 然而，这些观察的基础并不清楚。 虽然有益的 抗氧化剂的作用已被归因于防止氧化 修饰低密度脂蛋白（LDL）和抑制 动脉粥样硬化形成，其他因素也可能是重要的。 初步数据 本申请中提出的血小板功能依赖于 氧化应激和抗氧化保护之间的平衡。 在此建议的前两年，申请人将学习 抗氧化生物化学和自由基化学的指导下， 博士Balz Frei博士，这方面的资深调查员 的 申请人将参与博士已经在进行中的成功研究。 弗雷的实验室和开始，以具体解决的第一个目标， 建议;即，胞浆抗氧化状态对血小板的影响 功能和机制负责任何观察到的影响。 在 后三年，申请人将开始一段独立的时期 进一步研究生物化学和分子效应的研究 抗氧化剂对血小板功能的影响。 Joseph Loscalzo，医学博士，博士在此期间，申请人将：1） 表征膜抗氧化状态在调节血小板中的作用 功能和2）确定这些发现的体内相关性， 研究抗氧化剂缺乏或补充的动物模型。 工作 将为机制提供新的见解 抗氧化剂对血管疾病患者有益。 申请人的最终目标是追求的初步数据， 这项申请，并制定一个独立的研究计划，检查 细胞氧化还原状态、抗氧化剂和血管 体内平衡