Lipid Peroxidation and Antioxidant Mechanisms

脂质过氧化和抗氧化机制是NIEHS的竞争性更新建议 计划-2005年9月资助的项目。环境压力和生活方式对健康的影响 吸烟、酗酒在导致美国人死亡的疾病中扮演着重要角色 消费和不良饮食再加上其他环境因素会影响几种疾病的发生 疾病。氧化剂的形成是许多这些疾病的标志，而脂质过氧化是一种 各种环境侮辱的共同结果。事实上，氧化应激与 随着癌症和心血管疾病等各种病理疾病的出现，潜在的 环境应激与疾病发病机制之间的联系仍然不清楚。这些研究 这里提出的假设将检验不同的竞争氧化途径的平衡 脂质底物调控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使蛋白质加成改变细胞的假说 传递和调节与氧化应激有关的疾病。本计划项目包括四个 研究项目和一个紧密联系在一起的科学核心设施，将提供重要的见解 氧化和抗氧化剂在人类病理生理学中扮演的角色。项目1提供了一个 用于了解过氧化概况的机制框架，并领导提供 用于研究蛋白质亲和加合物的新型脂类亲和标记。项目2探索了化学和 二十碳五烯酸(EPA)的生物学，这是一种在鱼油中突出的脂肪酸，并探索了这一假说 EPA氧化产物可能对这种脂肪酸的生物学特性有很大贡献。 项目3评估了在细胞信号传递中起关键作用的亲电体，并提供了生物 用于研究整个细胞中的脂质亲和力标签的平台。项目4表明，二次亲电 脂质过氧化产物在氧化剂相关分子病理中起关键作用 探索鉴定和分析这些亲电体的蛋白质加合物的方法。所有的 这些项目具有高度的协作性，并高度依赖于脂肪组学分析科学 核心。

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.