Analysis of cerebral ischemic neural cell death and ferroptosis
| Project/Area Number |
19K07814
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Takasaki University of Health and Welfare (2021-2022)
Gunma University (2019-2020) |
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Principal Investigator |
Kubota Chisato 高崎健康福祉大学, 健康福祉学部, 助教 (90750638)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脳虚血 / フェロトーシス / 脂質過酸化 |
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| Outline of Research at the Start |
脳虚血による神経細胞死は活性酸素種の関与や酸化脂質の蓄積が知られ、2012年に提唱された新規細胞死「フェロトーシス」に特徴が似ている。フェロトーシスは鉄依存性の細胞死で、アポトーシスをはじめとする従来の細胞死とは異なる形態を示す。
本研究では、虚血性細胞死の培養細胞モデルを解析し、フェロトーシス実行に必須の脂質膜の過酸化連鎖反応を明らかにする。また新規マーカーを用いてマウスの脳虚血モデルを解析し、神経組織におけるフェロトーシス細胞死を確認する。脳虚血性神経細胞死の理解が進めば、脳梗塞をはじめとする脳神経疾患の予防や治療法の開発に繋がると期待できる。
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| Outline of Final Research Achievements |
Oxidative stress-associated cell death is implicated in cerebral ischemia-associated neural damage. Recently, a cell death pathway that involved reactive oxygen species production has been shown in tumor cells and named ferroptosis due to an iron-dependence. We revealed that lipoxygenase, intracellular free iron, and the accumulation of lipid reactive oxygen species are involved in glutamate induced cell death.
We found that volatilized 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) effectively prevented both ferroptosis and glutamate-induced oxidative toxicity in mouse neuronal cell line. Furthermore, TEMPO clearly reduced neural cell death in a middle cerebral artery occlusion (MCAO) model in mouse. We suggest potential physiological relevance of ferroptosis and neural cell injury during periods of ischemia.
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| Academic Significance and Societal Importance of the Research Achievements |
脳梗塞は時に致命的となる疾患で、脳組織障害の機序を明らかにし脳保護を果たす方法を示すことは社会的に重要である。本研究から、虚血による神経細胞死の機構の一端が明らかとなり、また神経保護剤として応用されうる化合物を示した。
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Report
(5 results)
Research Products
(9 results)
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[Presentation] 2,2,6,6-Tetramethylpiperidine-1-oxyl acts as a volatile inhibitor of ferroptosis and neurological injury2022
Author(s)
Hiroyuki Mizuno, Chisato Kubota, Yuta Takigawa, Ryosuke Shintoku, Masato Kanazawa, Yuhei Yoshimoto, Ichiro Koshiishi, Seiji Torii
Organizer
16th Congress of World Federation of Interventional and Therapeutic Neuroradiology(WFITN)
Related Report
Int'l Joint Research
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[Presentation] 2,2,6,6-テトラメチルピペリジン-1-オキシル(TEMPO)の 揮発投与によるフェロトーシス阻害及び脳保護効果2022
Author(s)
水野 寛之, 久保田 知里, 瀧川 裕太, 神徳 亮介, 金澤 雅人, 輿石 一郎, 好本 裕平, 鳥居 征司
Organizer
日本脳神経外科学会第81回学術総会
Related Report
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