ROLE OF PROTEIN NITRATION AND NITRIC OXIDE

蛋白质硝化和一氧化氮的作用

• 批准号: 6527305
• 负责人: FERID MURAD
• 金额: $ 29.81万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527305
• 关键词: biological signal transduction; laboratory mouse; laboratory rat; macrophage; neutrophil; nitric oxide; protein metabolism; protein purification; protein structure function; tyrosine

DESCRIPTION (Adapted from Investigator's Abstract: Tyrosine nitration has been shown in various pathological conditions of the cardiovascular system including ischemia-reperfusion injury (Liu 1997, Wang 1996), atherosclerosis (Leeuwenburgh 1997), myocardial inflammation (Kooy 1997), and circulatory shock (Fukuyama 1997); however, the physiological relevance of tyrosine nitration remains unclear. Furthermore, very little is known about the formation and metabolism of nitrotyrosine in vivo, including the conditions that favor nitration, the specificity of nitration, the reversibility of nitration and the fate of nitrated proteins. They hypothesize that tyrosine nitration/denitration is a regulated process which participates in signal transduction. Thus, understanding the metabolism of nitrotyrosine is important. In this study, they propose to study the formation, degradation, and reversibility of nitrotyrosine. To study tyrosine nitration they will first examine the conditions which favor tyrosine nitration to determine which nitrating species are responsible for nitration in vivo. The contribution of peroxynitrite and the myeloperoxidase system from neutrophils and macrophages will be studied. They will then determine which proteins are nitrated in vivo. By purifying and characterizing proteins that are nitrated in vivo, they can determine which proteins are vulnerable to nitration. The specificity of tyrosine nitration may give them a clue as to the physiological relevance of nitration. The fate of nitrated proteins is also of interest. If tyrosine nitration contributes to inflammatory injuries, the degradation of nitrated proteins or the removal of the nitrate group may contribute to the reparation of these injuries. Therefore, in the third and fourth specific aims they have proposed to study the degradation of nitrated proteins and the reversibility of tyrosine nitration. These experiments are designed to examine the formation and metabolism of nitrotyrosine; thus, this project should contribute to our understanding of both the physiologic and the pathologic role of tyrosine nitration.

描述（根据调查员的摘要：酪氨酸硝酸化已改编 在心血管系统的各种病理状况中显示 缺血再灌注损伤（Liu 1997，Wang 1996），动脉粥样硬化 （Leeuwenburgh 1997），心肌炎症（Kooy 1997）和循环冲击 （Fukuyama 1997）;但是，酪氨酸硝化的生理相关性 仍然不清楚。此外，关于形成和 硝基酪氨酸在体内的代谢，包括有利的条件 硝酸化，硝化的特异性，硝化的可逆性和 硝酸蛋白质的命运。他们假设酪氨酸硝化/否定 是一个参与信号转导的调节过程。因此， 了解硝基酪氨酸的代谢很重要。在这项研究中，他们 建议研究的形成，降解和可逆性 硝基酪氨酸。为了研究酪氨酸硝化，他们将首先检查 有利于酪氨酸硝化以确定哪种硝化物质的条件 负责体内硝化。过氧亚硝酸盐和 将研究来自中性粒细胞和巨噬细胞的髓过氧化物酶系统。 然后，他们将确定哪些蛋白在体内被硝化。通过净化和 表征体内硝化的蛋白质，他们可以确定哪个 蛋白质容易受到硝化的影响。酪氨酸硝化的特异性可能 给他们一个关于硝化的生理相关性的线索。命运 硝化蛋白也是感兴趣的。如果酪氨酸硝化有助于 炎症性损伤，硝酸蛋白质的降解或去除 硝酸盐组可能有助于赔偿这些伤害。 因此，在第三和第四个特定目标中，他们提出了研究 硝酸蛋白质的降解和酪氨酸的可逆性 硝化。这些实验旨在检查形成和 硝基酪氨酸的代谢；因此，这个项目应为我们的 了解酪氨酸的生理和病理作用 硝化。