2021 Fiscal Year Final Research Report
Remodeling of reactive sulfur metabolism by reactive oxygen species-producing enzyme, Nox: Discovery of reactive sulfur remodelase
| Project/Area Number |
20K21496
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
住本 英樹 九州大学, 医学研究院, 教授 (30179303)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | NAPDH oxidase (Nox) / Dual oxidase (Duox) / 活性硫黄分子 / グルタチオントリスルフィド / 統合硫黄メタボローム |
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| Outline of Final Research Achievements |
NADPH oxidase (Nox) is known as a major reactive oxygen species-producing enzyme in various organisms. We found that in HEK cells over-expressed with human Nox4, remarkable amount of various reduced forms of reactive persulfide species (RSS) like glutathione persulfide (GSSH) and dihydrogen persulfide (HSSH) are generated in the cells, and most intriguing thing is that sulfur is extended to become glutathione trisulfide (GSSSH), indicating the this is a unique sulfur oxido-reductase reaction. Our data therefore revealed for the first time that Nox eventually can function as NADPH-dependent sulfur oxidoreductase or RSS-producing or more strictly reactivating enzymes, through this very unique reduction and oxidation of the sulfur molecules.
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| Free Research Field |
硫黄生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、これまで世界のレドックス医学生物学のセントラルドグマとされてきた、Nox/Duoxが、本当は、硫黄代謝酵素であったというショッキングな事実に遭遇したことを端緒に、まったく未知の硫黄代謝経路である活性硫黄リモデリングの全容解明を目指すものであり、これまでの研究に例を見ない極めてチャレンジングで萌芽的な研究であるといえる。もちろん、これほど独創的な着想と発見は、世界の生命科学、医学領域において他の研究者の追随を許さない。
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