A novel function of hydrogen sulfide: Protection against heavy metal-induced neurotoxicity
| Project/Area Number |
17K08957
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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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| Research Field |
Applied pharmacology
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
Hara Hirokazu 岐阜薬科大学, 薬学部, 准教授 (30305495)
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| Co-Investigator(Kenkyū-buntansha) |
足立 哲夫 岐阜薬科大学, 薬学部, 教授 (40137063)
神谷 哲朗 岐阜薬科大学, 薬学部, 講師 (60453057)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 硫化水素 / 亜鉛 / 銅 / 神経細胞 / 酸化ストレス / 活性イオウ分子種 / 神経細胞死 / 活性酸素 / 神経細胞保護 / 細胞死 / 細胞保護作用 / 神経変性疾患 |
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| Outline of Final Research Achievements |
Zinc (Zn) aggravates brain damage after cerebral ischemia, since disturbance of zinc homeostasis in the brain induces neurotoxicity. Therefore, improvement of zinc disturbance may be a therapeutic approach for cerebral ischemia. Hydrogen sulfide (H2S) is involved in the detoxification of heavy metals. In this study, we found that H2S protected against Zn cytotoxicity in neuronal cells by preventing Zn influx into cells. Copper (Cu) is an essential trace element, whereas excess Cu is toxic to cells. We examined the effects of H2S on Cu cytotoxicity. Cu enhanced its cytotoxicity in the presence of H2S. The combination of Cu and H2S increased the amount of intracellular Cu compared with Cu alone. Thus, we concluded that the increased intracellular Cu accumulation elevates Cu cytotoxicity.
These findings suggest that H2S regulates the cellular dynamics of heavy metals.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の実施により、H2Sが神経細胞内外のZnやCu動態の制御因子として機能している可能性が示された。金属イオンの細胞内外の恒常性の破綻は、脳梗塞などの虚血性脳血管障害による神経細胞傷害以外に、アルツハイマー病やパーキンソン病などの神経変性疾患の発症とも密接に関連していることが報告されている。それゆえ、今回明らかとなったH2Sが金属イオンの細胞内動態を制御するというH2Sの新規機能は、神経変性疾患の病態解明のみならず、有効な治療薬が少ない神経変性疾患の新規治療薬の開発にも繋がる重要な知見となると考えられる。
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Report
(4 results)
Research Products
(14 results)
