2017 Fiscal Year Final Research Report
Pathophysiological role of NO-induced calcium release in skeletal muscle
| Project/Area Number |
15K08227
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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 |
General pharmacology
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| Research Institution | Toho University (2016-2017)
The University of Tokyo (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 一酸化窒素 / リアノジン受容体 / カルシウム / 骨格筋 / 神経細胞死 / NICR / S-ニトロシル化 |
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| Outline of Final Research Achievements |
The type 1 ryanodine receptor (RyR1) is predominantly expressed in the skeletal muscle and brain. Nitric oxide (NO) induces calcium release from sarcoplasmic/endoplasmic reticulum through S-nitrosylation of Cys at 3636 (Cys-3636) in RyR1. In order to elucidate the pathophysiological role of NO-induced calcium release (NICR) in vivo, we generated a knock-in (KI) mouse line, in which the Cys-3636 was replaced by Ala to prevent its S-nitrosylation. We showed that NICR was silenced in both neurons and skeletal muscle cells from KI mice. However, the exercise function of KI mice was not altered. In the brain, we provided evidence that NICR exacerbates neurodegeneration in the hippocampus following epileptic seizures, suggesting that RyR1 is a promising therapeutic target candidate to ameliorate the neurodegenerative effect of status epilepticus.
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| Free Research Field |
生理学、薬理学
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