The mechanism of oxidative neuronal injury induced by methylmercury.(Fostering Joint International Research)
| Project/Area Number |
15KK0024
|
|---|
| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Risk sciences of radiation and chemicals
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
Vogel Christoph University of California, Davis, Center for Health and the Environment, Research Professor
Haarmann-Stemmann Thomas Leibniz Research Institute for Environmental Medicine
|
|---|
| Project Period (FY) |
2016 – 2018
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
|
|---|
| Keywords | 芳香族炭化水素受容体 / ミクログリア / マクロファージ / 酸化ストレス / 炎症 / 炎症反応 / AhR / NADPH oxidase / 環境化学物質 / 脳内炎症 |
|---|
| Outline of Final Research Achievements |
In this study, we aimed to elucidate the mechanism by which aryl-hydrocarbon receptor (AhR) regulates neuronal oxidative stress. From the global analysis, it was revealed that p47phox, a subunit of NADPH oxidase, was upregulated by AhR. p47phox has two dioxin-response elements (DREs) in its promoter region and AhR could bind to both DREs. Oxidative stress induced by AhR was due to increases in p47phox expression. IL-33, a proinflammatory cytokine, was also upregulated by AhR. Two DREs are in the IL-33 promoter region and one of these was responsible for AhR. Together, AhR can be involved in oxidative neuronal injury via activation of NADPH oxidase and upregulation of inflammatory cytokines.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、メチル水銀をはじめとした化学物質によるAhRを介した酸化的神経障害メカニズムを示すものである。AhRは、ダイオキシン類の受容体であり、リガンドが結合すると代謝酵素の発現を上昇させる解毒に関わる転写因子としての一面が良く研究されているが、本研究から、AhRが酸化ストレスのレギュレーターとなり、また炎症反応を制御するという従来とは異なる役割が示される。化学物質による神経毒性メカニズムが明らかになることにより、化学物質に感受性の高いグループが同定できるため、化学物質の使用に際してオーダーメイドの対策が可能となり、化学物質による障害の予防にも役立つ。
|
Report
(4 results)
Research Products
(16 results)
