| Project/Area Number |
26713024
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Legal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Unuma Kana 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (30586425)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2015: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2014: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | 敗血症 / オートファジー / 心臓 / 一酸化炭素 / ヘムオキシゲナーゼ / 肝臓 / 酸化ストレス |
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| Outline of Final Research Achievements |
Lipopolysaccharide (LPS)-induced myocardial dysfunction is caused, in part, by mitochondrial dysfunction. In this study, we show that CoPPIX not only accelerates the autophagic response but also promotes lysosome reformation in the rat heart treated with LPS. Activation of TFEB was also observed, indicating a hyper consumption and subsequent reformation of the lysosome to meet the increased demand for autophagosome cleaning. CoPPIX was found to promote these processes and tended to restore the LPS-induced suppression of cardiac performances whilst chloroquine abrogates these beneficial effects. The cardioprotective effect of CoPPIX against LPS toxicity was also observed via decreased levels of cardiac releasing enzymes in the plasma. Taken together, our current data indicate that lysosome reformation mediated by TFEB may be involved in cardioprotection against LPS-induced septic insults, and serve as a novel mechanism by which CoPPIX protects the heart against oxidative stress.
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