| Project/Area Number |
26282198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Ohta Shigeo 日本医科大学, 医学(系)研究科(研究院), 教授 (00125832)
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| Co-Investigator(Renkei-kenkyūsha) |
KAMIMURA Naomi 日本医科大学, 先端医学研究所, 准教授 (60283800)
WOLF Alexander 日本医科大学, 先端医学研究所, 講師 (20434136)
IUCHI Katsuya 日本医科大学, 先端医学研究所, 助教 (40553847)
NISHIMAKI Kiyomi 日本医科大学, 先端医学研究所, その他 (00465345)
ICHIMIYA Harumi (YOKOTA Takashi) 日本医科大学, 先端医学研究所, その他 (40553251)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 分子状水素 / 遺伝子発現制御 / 情報伝達機構 / 生活習慣病 / 酸化脂質 / 脂質メディエーター / ミトコンドリア / 酸化ストレス / 水素 |
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| Outline of Final Research Achievements |
We previously reported that molecular hydrogen (H2) acts as a novel antioxidant to exhibit multiple functions. H2 regulates various signal transduction pathways and the expression of many genes for health-care and the prevention of life style related diseases. However, the primary targets of H2 in the signal transduction pathways are unknown. Here, we attempted to determine how H2 regulates gene expression.
We found that H2 regulates gene expression via the Ca(2+) signal transduction pathway by modifying the free radical-dependent generation of oxidized phospholipid mediators. This mechanism explains the decrease in inflammatory cytokines. In addition, to suppress metabolic syndrome,H2 induces expression of the PGC-1α gene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism. The expression of PGC-1α might be regulated indirectly through sequential regulation by H2, 4-hydroxy-2-nonenal, and Akt/FoxO1 signaling.
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