ROLE OF PROTEIN NITRATION AND NITRIC OXIDE

描述(改编自调查者摘要：酪氨酸硝化已被 表现为心血管系统的各种病理状态，包括 缺血再灌注损伤(Liu 1997，Wang 1996)，动脉粥样硬化 (Leeuwenburgh 1997)、心肌炎(Kooy 1997)和循环系统休克 (Fukuyama 1997)；然而，酪氨酸硝化的生理相关性 目前仍不清楚。此外，人们对它的形成和发展知之甚少 硝基酪氨酸在体内的代谢，包括有利于 硝化作用、硝化作用的特殊性、硝化作用的可逆性以及 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， 了解硝基酪氨酸的代谢是很重要的。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作用，他们首先要研究 有利于酪氨酸硝化以确定哪些硝化物种的条件 负责体内的硝化作用。过氧亚硝酸盐的贡献和 将研究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。通过提纯和 对体内硝化的蛋白质进行表征，他们可以确定 蛋白质很容易被硝化。酪氨酸硝化的特异性可能 给他们一个关于硝化作用的生理相关性的线索。中国人的命运 硝化蛋白质也令人感兴趣。如果酪氨酸硝化作用有助于 炎性损伤，硝化蛋白的降解或清除 硝酸基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 硝化蛋白质的降解与酪氨酸的可逆性 硝化作用。这些实验被设计用来检查形成和 硝基酪氨酸的代谢；因此，这个项目应该有助于我们的 对酪氨酸的生理和病理作用的认识 硝化作用。

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.