Research Project
Grant-in-Aid for Scientific Research (C)
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.
All 2018 2017 2016 2015 Other
All Journal Article (6 results) (of which Peer Reviewed: 6 results, Open Access: 4 results, Acknowledgement Compliant: 3 results) Presentation (22 results) (of which Int'l Joint Research: 1 results, Invited: 1 results) Remarks (5 results)
Antioxid Redox Signal (in press)
Volume: - Issue: 12 Pages: 1147-1157
10.1089/ars.2018.7498
脳科学辞典
Volume: ‐
Eur. J. Neurosci.
Volume: 44 Issue: 3 Pages: 2004-2014
10.1111/ejn.13285
EBioMedicine.
Volume: 11 Pages: 253-261
10.1016/j.ebiom.2016.08.020
International Journal of Molecular Sciences
Volume: 17 Issue: 10 Pages: 1652-1652
10.3390/ijms17101652
120005997697
Life Sciences
Volume: 139 Pages: 69-73
10.1016/j.lfs.2015.08.005
https://www.toho-u.ac.jp/med/lab/lab_uniphysio.html
http://gyoseki.toho-u.ac.jp/thuhp/KgApp
http://www.toho-u.ac.jp/med/lab/lab_uniphysio.html
http://calcium.cmp.m.u-tokyo.ac.jp