Verification of reduction of superoxide toxicity by nitric oxide (NO) synthase and exogenous NO

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Yamagata University
• Principal Investigator: Fujii Junichi 山形大学, 大学院医学系研究科, 教授 (00222258)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 一酸化窒素 / スーパーオキシド / ペルオキシ亜硝酸イオン / マクロファージ

Outline of Final Research Achievements

Nitric oxide (NO) increases cGMP by binding to the heme of guanylate cyclase in vascular smooth muscle cells and exerts a vasorelaxant effect. On the other hand, reactive oxygen species derived from superoxide causes oxidative damage, so it is important to keep the amount low for maintaining health. Until now, the peroxynitrite ion produced by the reaction of NO and superoxide has been considered to be an unfavorable reaction because peroxynitrite ion is extremely harmful. However, this study with mouse macrophages suggests that the usefulness of NO-mediated superoxide elimination outweighs toxicity of peroxynitrite ions, which are produced only limited amounts under physiological conditions.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

これまでペルオキシ亜硝酸イオンの細胞毒性が重要視されるあまり、NOによるスーパーオキシド消去はむしろ有害とされてきた。今回の研究結果は、体内で生成する程度のNOは活性酸素の量を減らし、むしろ酸化障害を抑えるため様々な病態の改善に働く可能性を示唆している。
今後こうした視点に基づいたNOの研究が進むことで、活性酸素の関わる炎症性疾患などにおけるNOを対象とする治療戦略に新たな進展が期待される。