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（改编自研究者摘要：酪氨酸硝化已被 表现在心血管系统的各种病理状态中， 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）和循环性休克 （Fukuyama 1997）;然而，酪氨酸硝化的生理相关性 仍不清楚此外，人们对它的形成知之甚少， 硝基酪氨酸在体内的代谢，包括有利于硝基酪氨酸代谢的条件。 硝化反应的专一性、硝化反应的可逆性和硝化反应的 硝化蛋白质的命运他们假设酪氨酸硝化/反硝化 是一个参与信号转导的调节过程。因此，在本发明中， 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 有利于酪氨酸硝化的条件，以确定哪种硝化物质 负责体内的硝化作用。过氧亚硝酸根和 将研究来自嗜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质在体内被硝化。通过净化和 表征在体内被硝化的蛋白质，他们可以确定 蛋白质易被硝化。酪氨酸硝化的特异性可能 给了他们一个硝化作用的生理意义的线索。的命运 硝化蛋白也是令人感兴趣的。如果酪氨酸硝化有助于 炎症损伤，硝化蛋白质的降解或 硝酸盐基团可能有助于这些损伤的修复。 因此，在第三和第四个具体目标中，他们提出要研究 硝化蛋白质的降解和酪氨酸的可逆性 硝化作用。这些实验的目的是检查形成和 硝基酪氨酸的代谢;因此，这个项目应该有助于我们的 了解酪氨酸的生理和病理作用 硝化作用。