Dynamics of nitric oxide (NO) in biological miliue and mechanism of NO-induced injury.

生物环境中一氧化氮（NO）的动态及NO诱导损伤的机制。

• 批准号: 09470174
• 负责人: NAKAZAWA Hiroe
• 金额: $ 1.22万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470174/
• 关键词: nitric oxide; superoxide; peroxynitrite; NO synthase; cytotoxicity; brain ischemia; endotoxin-shock; nitrotyrosine

An increasing evidence shows extreamely diverse biological functions of NO.However its dynamics in bIological system is not clealy defined due to its short life and low concentration. Furthermore the mechanism of cytotoxic aspect of NO has not been elucidated.The purposes of this study were 1) to examine the reaction of NO and superoxide since both react each other at a diffusion-limited rate and form peroxynitrite. All of these are potent cytotoxic molecules. 2) to measure productions of NO, superoxide and peroxynitrite in in vitro system using culture cells and in in vivo system using rats. And 3) to demonstrate the role of peroxynitrite in diseases by measuring nitrotyrosine formation as a footprint of peroxynitrite-induced injury in patients who are suffering from endotoxin shock or from chronic allergic rhinitis.Results1) Among these NO synthase (bNOS, iNOS, eNOS) the flux of NO from INOS is the most rapid.2) The generation of superoxide from NO synthases was successful and the kinetics of electron flow in the NOS were clarified.3) Nitrotyrosine formation was demonstrated in patients with endotoxin shock or allergic rhinitis.

越来越多的证据表明NO具有极其多样的生物学功能，但由于其存在时间短、浓度低，其在生物系统中的动态尚不清楚。本研究的目的是：1）研究NO与超氧阴离子的反应，因为两者以扩散限制速率相互反应并形成过氧亚硝酸盐。所有这些都是有效的细胞毒性分子。2)采用体外培养细胞系统和大鼠体内系统测定NO、超氧阴离子和过氧亚硝酸根的产生。3）通过检测内毒素休克或慢性变应性鼻炎患者中过氧化亚硝酸盐损伤的足迹--硝基酪氨酸的形成，来证明过氧化亚硝酸盐在疾病中的作用（bNOS，iNOS，eNOS）NO从INOS流出最快。NO还原酶成功地产生了超氧化物，并阐明了NOS中电子流的动力学。3）在内毒素休克或变应性鼻炎患者中证实了硝基酪氨酸的形成。

项目成果

Zhi Su: "Peroxynitrite is not major mediator of endotherial cell injury by activated neutrophils in vitro." Cardiovasc Res. 39. 485-491 (1998)

苏志：“过氧亚硝酸盐不是体外激活的中性粒细胞损伤内皮细胞的主要介质。”

Tanaka Y: "Medical Applications of Synchrotron Radiation" Ando M, Uyama C, 5 (1998)

田中 Y：“同步辐射的医学应用” Ando M、Uyama C，5 (1998)

Genka C: Method of Cardiac Research II. Roppou Publishers, 8 (1998)

Genka C：心脏研究方法 II。

Hoshiai K: Review in Antioxidants. Sentanigakusha, 7 (1998)

Hoshiai K：抗氧化剂评论。

Hoshiai M: "Impaired sarcoplasmic reticulim function in lipopolysaccharide-induced myocardial dysfunction." Shock. (in press).

Hoshiai M：“脂多糖引起的心肌功能障碍中肌浆网功能受损。”