Lipid Peroxidation and Antioxidant Mechanisms

描述(由申请人提供) NIEHS计划-项目：脂质过氧化和抗氧化机制汇集了四位经验丰富的研究人员，他们对脂质的自由基化学和生物学、过氧化、抗氧化剂以及细胞损伤和保护机制有共同的兴趣。在美国，环境压力和生活方式在疾病中起着重要作用，这些疾病对死亡率有很大影响。吸烟、饮酒和不良饮食与其他环境因素相结合，会影响几种疾病的发病率。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侮辱的共同结果。事实上，氧化应激与癌症和心血管疾病等各种病理疾病的发生密切相关。环境中的化学和物理因素都会促进生物系统中的脂质过氧化和氧化损伤。这些过程会导致器官功能障碍、遗传毒性和疾病。然而，将环境压力与疾病发病机制联系起来的潜在机制仍然不清楚。本文提出的研究将确定各种脂质前体的氧化损伤和损伤机制。该计划项目包括四个研究项目和一个紧密联系在一起的仪器核心(蛋白质组学/质谱学)，这将为氧化和抗氧化剂在人类病理生理学中所起的作用提供重要的见解。项目1检验了不同脂类和分子物种的过氧化具有显著不同后果的假设，并制定了获得过氧化形成的重要产物的轮廓的协议。项目2探索了二十碳五烯酸(EPA)的化学和生物学，这是一种在鱼油中突出的脂肪酸，并探索了EPA氧化产物可能对这种脂肪酸的生物学特性有重要贡献的假设。项目3利用高通量筛选探索在脂质过氧化过程中形成的亲电体的化学和生物学，并确定这些亲电体的蛋白质靶标。项目4认为，脂质氧化的次级亲电产物在氧化剂相关的分子病理学中起着关键作用，并探索了鉴定和分析这些亲电体的蛋白质加合物的方法。所有项目都高度协作，高度依赖设施核心。

DESCRIPTION (provided by applicant) The NIEHS Program-Project: Lipid Peroxidation and Antioxidant Mechanisms brings together four experienced investigators who share an interest in the free radical chemistry and biology of lipids, peroxidation, antioxidants and mechanisms of cellular injury and protection. Environmental stress and lifestyle play an important role in diseases that contribute significantly to mortality in the United States. 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. Both chemical and physical factors in the environment promote lipid peroxidation and oxidative damage in biological systems. These processes lead to organ dysfunction, genotoxicity, and disease. Nevertheless, the underlying mechanisms linking environmental stresses with disease pathogenesis remain obscure. The studies proposed here will identify mechanisms of oxidative damage and injury for a variety of lipid precursors. This Program Project includes four research projects and one instrument core (proteomics/mass spectrometry) in a tightly knit group that will provide important insights into the role that oxidation and antioxidants play in human pathophysiology. Project 1 tests the hypothesis that the peroxidation of different lipid classes and molecular species has dramatically different consequences and lays out protocols for obtaining profiles of important products formed in peroxidation. 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 explores the chemistry and biology of electrophiles formed in lipid peroxidation by the use of high throughput screens and identifies protein targets of these electrophiles. Project 4 suggests that secondary electrophilic products of lipid oxidation 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 facility cores.