Role of NADPH oxidase on brain damage due to carbon monoxide

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: Hara Shuichi 東京医科大学, 医学部, 准教授 (70208651)
• Research Collaborator: Kuriiwa Fumi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 一酸化炭素中毒 / 活性酸素 / ヒドロキシルラジカル / ラット線条体 / NADPH oxidase / アンジオテンシンII

Outline of Final Research Achievements

Carbon monoxide (CO) poisoning stimulates generation of reactive oxygen species, such as cytotoxic hydroxyl radical (OH), which plays a role in brain damage due to CO poisoning. The present results suggest that OH generation may be mediated through activation of NADPH oxidase (NOX) isoforms dependent on Rac (RAS-related C3 botulinus toxin substrate), such as NOX1 and NOX2, via cAMP signaling pathways and through activation of renin-angiotensin system (RAS), which is independent of the cAMP signaling pathways followed by NOX activation. Interference with the RAS with angiotensin II type 1 receptor antagonists or angiotensin converting enzyme inhibitors, which are clinically used with high safety, might be a novel therapeutic strategy for patients with CO poisoning.

Free Research Field

中毒学

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、一酸化炭素(CO)中毒による脳損傷に深く関与する脳内活性酸素の生成には、cAMPシグナル伝達系経由のRac依存性NADPH oxidase活性化を介する経路だけでなく、これとは異なるレニン-アンジオテンシン系の活性化を介する経路も存在することが明らかとなった。そのため、臨床で広く使用され、安全性も確立されているアンジオテンシンII受容体遮断薬およびアンジオテンシン変換酵素阻害薬によるCO中毒治療の可能性が示唆された。