NITRIC OXIDE SYNTHESIS AND N-NITROSATION IN NEUTROPHILS

在过去的几年里，一氧化氮(NO)已经成为一种重要的 在几个关键的生理过程中发挥调节作用。一般情况下，当 合成用于血管内稳态，神经元通讯，和 免疫系统功能一氧化氮水平受到严格控制。在……里面 此外，持续或升高的NO合成可能是有害的 可能在内毒素休克、炎症相关的病因学中起重要作用 组织损伤、神经元病理与N-亚硝胺诱导 致癌。此外，一氧化氮可导致人类细胞和 细菌与DNA发生脱氨基反应。诱导型一氧化氮合酶已经被 被认为是持续NO形成的来源。受体 由构成酶介导的NO生成反应 兴奋性氨基酸谷氨酸现在令人兴奋，但它开启了 通向关于这种活性物质的毒性的一些重要问题 分子。这个项目的总体长期目标是一个彻底的 生物条件下NO反应性的表征。 对这种反应性的了解是疾病状态不可或缺的一部分 由高水平和持续的一氧化氮合成带来的。具体的 本项目的目标如下：反应的目标，(2) 中性粒细胞一氧化氮合酶的特征，(3)过氧化物酶和髓过氧化物酶的研究 与NO的催化反应和亚硝化反应，(4)研究非 针对NO的靶细胞防御系统，(5)为其他 项目包括：小鼠巨噬细胞一氧化氮合酶(NOS)的cDNAs N-烷基-L-精氨酸协同肝脏表达实验 作为一氧化氮合酶抑制剂的衍生物和抗一氧化氮合酶多克隆抗体 诱导型一氧化氮合酶。

Over the last several years nitric oxide (NO) has emerged as an important mediator in several key physiological processes. In general, when synthesized for blood vessel homeostasis, neuronal communication, and immune system function the levels of NO are tightly controlled. In addition, sustained or elevated synthesis of NO can be deleterious and may be important in the etiology of endotoxic shock, inflammation-related tissue damage, neuronal pathology and N-nitrosamine-induced carcinogenesis. Furthermore, NO can cause mutations in human cells and bacteria via deamination reactions with DNA. The inducible NOS has been implicated as the source of the sustained NO formation. Receptor mediated NO formation by the constitutive enzyme in response to the excitatory amino acid glutamate has now been exciting but has opened the door to some important questions regarding the toxicity of this reactive molecule. The overall long-term goal for this project is a thorough characterization of the reactivity of NO under biological conditions. An understanding of this reactivity is integral to the disease states brought about by high and sustained levels of NO synthesis. The specific aims of this project are as follows: The aims of this reactions, (2) characterize the neutrophil NOS, (3) study peroxidase and myeloperoxidase catalyzed reactions with NO and nitrosation reactions, (4) study non- target cell defense systems against NO, (5) provide key reagents to other projects including: cDNA for the murine macrophage NO synthase (NOS) for the collaborative liver expression experiments, N-alkyl-L-arginine derivatives as inhibitors for the NOS, and polyclonal antibodies against the inducible NOS.