Antioxidants and oxidative damage in mitochondria

线粒体中的抗氧化剂和氧化损伤

基本信息

批准号：
7010952
负责人：
CECILIA GIULIVI
金额：
$ 14.8万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-23 至 2007-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7010952
关键词：
DNA damage antioxidants cell component structure /function cytotoxicity dietary constituent flavonoids laboratory rat mitochondria nitrates nitration nutrition related tag oxidative stress tyrosine vegetables

项目摘要

DESCRIPTION (provided by applicant): The focus of this project resides on the role of small antioxidant molecules on the prevention and/or repair of nitrated proteins in mitochondria. Protein nitration occurs in biological systems exposed to nitric oxide. The addition of a nitro group to a tyrosine residue, yielding 3-nitrotyrosine, has been claimed to be a posttranslational modification, part of signal transduction pathways, or a result of "normal" oxidative stress. In this study, we will characterize the mechanism underlying the nitration of proteins in nitric oxide-producing mitochondria, given the important role that these organelles have in the maintenance of cellular ATP, beta-oxidation, heme synthesis, and other functions. Our studies will be aimed at understanding the kinetic and structural changes caused by nitration, and how naturally occurring antioxidants -- present in fruits and vegetables may prevent/reverse this effect. The antioxidant effect of flavonoids, coumarins, and catechins will be studied in terms of hydroxyl substitution, conjugation of rings, and o-methylation of hydroxyl groups to elucidate an association between structure and function. To this end, the specific aims of this proposal are the following: 1. Investigate the molecular mechanisms of mitochondrial protein nitration 2. Elucidate the biological relevance of protein nitration in mitochondria 3. Structure-activity association of naturally occurring flavonoids in the abrogation of protein nitration, and 4. Bioavailability of flavonoids containing diets in nitrative stress.

描述（由申请人提供）：该项目的重点在于小抗氧化剂分子在预防和/或修复线粒体硝化蛋白质中的作用。蛋白质硝化发生在暴露于一氧化氮的生物系统中。酪氨酸残基上添加硝基，产生 3-硝基酪氨酸，被认为是翻译后修饰、信号转导途径的一部分或“正常”氧化应激的结果。在这项研究中，我们将描述产生一氧化氮的线粒体中蛋白质硝化的机制，因为这些细胞器在维持细胞 ATP、β-氧化、血红素合成和其他功能方面发挥着重要作用。我们的研究旨在了解硝化引起的动力学和结构变化，以及水果和蔬菜中天然存在的抗氧化剂如何预防/逆转这种影响。将从羟基取代、环共轭和羟基邻甲基化方面研究类黄酮、香豆素和儿茶素的抗氧化作用，以阐明结构和功能之间的关联。为此，本提案的具体目标如下： 1. 研究线粒体蛋白质硝化的分子机制 2. 阐明线粒体中蛋白质硝化的生物学相关性 3. 天然黄酮类化合物在消除蛋白质硝化中的结构-活性关联，以及 4. 硝化胁迫下含类黄酮饮食的生物利用度。