Lipid Peroxidation and Antioxidant Mechanisms

脂质过氧化和抗氧化机制

• 批准号: 7900675
• 负责人: Ned Allen Porter
• 金额: $ 38.64万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7900675
• 关键词: Lipid; Peroxidation; Antioxidant; Mechanisms

Lipid Peroxidation and Antioxidant Mechanisms is a competitive renewal proposal for an NIEHS Program- Project that was funded in September of 2005. Environmental stress and lifestyle play an important role in diseases that contribute significantly to mortality in the U.S. Cigarette smoking, alcohol consumption and poor diet combine with other environmental factors to affect the incidence of several diseases. The formation of oxidants is a hallmark of many of these diseases and lipid peroxidation is a common result of diverse environmental insults. Indeed, oxidative stress has been closely associated with the onset of pathologies as diverse as cancer and cardiovascular disease. The underlying mechanisms linking environmental stresses with disease pathogenesis remain obscure. The studies proposed here will test the hypothesis that the balance of competing oxidation pathways for different lipid substrates governs adaptation to oxidative stress and oxidative injury. The Program Project also directly addresses the hypothesis that protein adduction by lipid peroxidation products alters cellular signaling and modulates diseases linked to oxidative stress. This Program Project includes four research projects and one scientific core facility in a tightly-knit group that will provide important insights into the role that oxidation and antioxidants play in human pathophysiology. Project 1 provides a mechanistic framework for understanding peroxidation profiles and leads the chemistry that provides novel lipid affinity-tags for studying protein-electrophile adducts. Project 2 explores the chemistry and biology of eicosapentaenoic acid (EPA), a fatty acid prominent in fish oil, and explores the hypothesis that EPA oxidation products may contribute significantly to the biological properties of this fatty acid. Project 3 evaluates electrophiles that play critical roles in cell signaling and provides the biological platform for studying lipid affinity tags in whole cells. Project 4 suggests that secondary electrophilic products of lipid peroxidation play critical roles in oxidant-associated molecular pathologies and explores methodologies for identification and analysis of protein adducts of these electrophiles. All of the projects are highly collaborative and are highly dependent on the Lipidomics Analysis scientific core.

脂质过氧化和抗氧化机制是 NIEHS 的一项有竞争力的更新提案 计划 - 2005 年 9 月资助的项目。环境压力和生活方式发挥着重要作用 在导致美国死亡率显着增加的疾病中，吸烟、酗酒具有重要作用 消费和不良饮食与其他环境因素相结合，影响几种疾病的发病 疾病。氧化剂的形成是许多此类疾病的标志，而脂质过氧化是 各种环境侵害的共同结果。事实上，氧化应激与 随着癌症和心血管疾病等多种疾病的出现。底层的 将环境压力与疾病发病机制联系起来的机制仍然不清楚。研究 这里提出的将测试以下假设：不同的竞争氧化途径的平衡 脂质底物控制对氧化应激和氧化损伤的适应。该计划项目还 直接解决了脂质过氧化产物的蛋白质加合改变细胞的假设 信号传导并调节与氧化应激相关的疾病。该计划项目包括四个 一个紧密结合的团队中的研究项目和一个科学核心设施将提供重要的见解 研究氧化和抗氧化剂在人类病理生理学中的作用。项目1提供了一个 用于理解过氧化谱的机制框架并引导提供的化学 用于研究蛋白质亲电子加合物的新型脂质亲和标签。项目 2 探索化学和 二十碳五烯酸 (EPA)（鱼油中常见的一种脂肪酸）的生物学，并探讨了这一假设 EPA 氧化产物可能对该脂肪酸的生物特性有显着贡献。 项目 3 评估在细胞信号传导中发挥关键作用的亲电子试剂，并提供生物 研究全细胞中脂质亲和标签的平台。项目4表明二级亲电子 脂质过氧化产物在氧化剂相关的分子病理学中起关键作用 探索了鉴定和分析这些亲电子试剂的蛋白质加合物的方法。所有的 这些项目是高度协作的，并且高度依赖于脂质组学分析科学 核。