Lipid Peroxidation and Antioxidant Mechanisms

脂质过氧化和抗氧化机制

基本信息

批准号：
8294727
负责人：
Ned Allen Porter
金额：
$ 145.95万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-12 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8294727
关键词：
Accounting Address Affect Affinity Alcohol consumption Alkynes Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Arachidonic Acids Area Atherosclerosis Basic Science Biological Biological Assay Biological Markers Biology Cardiovascular Diseases Cell physiology Cells Cellular biology Characteristics Chemicals Chemistry Clinical Research Complex Core Facility Cultured Cells Data Development Diet Disease Disease model Eicosapentaenoic Acid Environmental Exposure Environmental Risk Factor Equilibrium Esters Event Fatty Acids Fish Oils Fostering Free Radicals Functional disorder Funding Gene Expression Goals Grant Head Human In Vitro Incidence Individual Inflammatory Injury International Isoprostanes Journals Laboratories Life Style Link Lipid Biochemistry Lipid Peroxidation Lipids Low Density Lipoprotein Receptor Malignant Neoplasms Mass Spectrum Analysis Mediator of activation protein Metabolism Methodology Methods Molecular Mus National Institute of Environmental Health Sciences Nucleic Acids Oxidants Oxidative Stress Pathogenesis Pathology Pathway interactions Phospholipids Plasma Cells Play Polyunsaturated Fatty Acids Post-Translational Protein Processing Procedures Process Property Protein Analysis Protein Biochemistry Proteins Proteomics Protocols documentation Publications Research Research Personnel Research Project Grants Role Sampling Scientist Signal Pathway Signal Transduction Sorting - Cell Movement Space Maintenance Stress Study Section Supplementation Talents Technology Testing United States National Institutes of Health Universities adduct base cigarette smoking disorder prevention editorial experience human disease in vivo insight instrumentation macrophage meetings member molecular pathology mortality new technology novel oxidation oxidized lipid peroxidation programs protein function research facility research study response skills

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：脂质过氧化和抗氧化机制是 NIEHS 项目的一项竞争性更新提案，该项目于 2005 年 9 月资助。环境压力和生活方式在导致美国死亡的疾病中发挥着重要作用。吸烟、饮酒和不良饮食与其他环境因素共同影响多种疾病的发生。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损害的常见结果。事实上，氧化应激与癌症和心血管疾病等多种疾病的发生密切相关。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。这里提出的研究将检验以下假设：不同脂质底物的竞争性氧化途径的平衡控制对氧化应激和氧化损伤的适应。该计划项目还直接提出了这样的假设：脂质过氧化产物的蛋白质加合会改变细胞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研究项目和一个紧密结合的科学核心设施，将为了解氧化和抗氧化剂在人类病理生理学中的作用提供重要见解。项目 1 提供了一个用于理解过氧化谱的机制框架，并引领了为研究蛋白质-亲电子加合物提供新型脂质亲和标签的化学过程。项目 2 探讨了二十碳五烯酸 (EPA)（一种鱼油中常见的脂肪酸）的化学和生物学，并探讨了 EPA 氧化产物可能对这种脂肪酸的生物特性做出重大贡献的假设。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，并为研究全细胞中的脂质亲和标签提供生物平台。项目 4 表明，脂质过氧化的次级亲电子产物在氧化剂相关的分子病理学中发挥着关键作用，并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。所有项目都是高度协作的，并且高度依赖脂质组学分析科学核心。

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rate constants for peroxidation of polyunsaturated fatty acids and sterols in solution and in liposomes.

DOI：
10.1021/ja9029076
发表时间：
2009-09-16
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Xu L;Davis TA;Porter NA
通讯作者：
Porter NA

Oxysterols from free radical chain oxidation of 7-dehydrocholesterol: product and mechanistic studies.

DOI：
10.1021/ja9080265
发表时间：
2010-02-24
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Xu, Libin;Korade, Zeljka;Porter, Ned A.
通讯作者：
Porter, Ned A.

Sequence tagging reveals unexpected modifications in toxicoproteomics.

DOI：
10.1021/tx100275t
发表时间：
2011-02-18
期刊：
Chemical research in toxicology
影响因子：
4.1
作者：
Dasari S;Chambers MC;Codreanu SG;Liebler DC;Collins BC;Pennington SR;Gallagher WM;Tabb DL
通讯作者：
Tabb DL

Assay of protein and peptide adducts of cholesterol ozonolysis products by hydrophobic and click enrichment methods.

通过疏水和点击富集方法测定胆固醇臭氧分解产物的蛋白质和肽加合物。

DOI：
10.1021/tx500229h
发表时间：
2014
期刊：
Chemical research in toxicology
影响因子：
4.1
作者：
Windsor,Katherine;Genaro-Mattos,ThiagoC;Miyamoto,Sayuri;Stec,DonaldF;Kim,Hye-YoungH;Tallman,KeriA;Porter,NedA
通讯作者：
Porter,NedA

Identification of the peroxidation products of 13-hydroxy-gamma-linolenate and 15-hydroxyarachidonate: mechanistic studies on the formation of leukotriene-like diols.

13-羟基-γ-亚麻酸酯和15-羟基花生四烯酸酯的过氧化产物的鉴定：白三烯样二醇形成的机理研究。