Research Project
Grant-in-Aid for Scientific Research (C)
Glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a homotetrameric protein that also mediates cell death under oxidative stresses. We previously reported that intermolecular disulfide-bonding GAPDH aggregates through oxidation of the active site cysteine (Cys-152) participate in oxidative stress-induced cell death. We also revealed that the active site cysteine-null GAPDH (C152A-GAPDH) rescues oxidative stress-induced neuronal cell death in a dominant negative manner via the formation of these hybrid tetramer both in vitro and in vivo. Here we report that this dominant negative C152A-GAPDH mutant against endogenous GAPDH aggregation in response to oxidative stress ameliorated neuronal cell death in neurological models using a specific inhibitor of GAPDH aggregation (GAI-X) exerted decrease of neurological dysfunctions. These findings provide a therapeutic avenue of new drug target for the brain damages such as Stroke and Alzheimer disease.
All 2016 2015 2013 Other
All Journal Article (5 results) (of which Int'l Joint Research: 1 results, Peer Reviewed: 5 results, Open Access: 3 results, Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)
Nitric Oxide
Volume: 53 Pages: 13-21
10.1016/j.niox.2015.12.005
Biochem Biophys Res Commun.
Volume: 2015 Issue: 2 Pages: 373-376
10.1016/j.bbrc.2015.09.150
J. Biol. Chem.
Volume: 290 Issue: 43 Pages: 26072-26087
10.1074/jbc.m115.669291
The Journal of Biological Chemistry
Volume: 290 Issue: 1 Pages: 56-64
10.1074/jbc.m114.596205
Volume: VOL. 290 Issue: 23 Pages: 14493-14503
10.1074/jbc.m114.635607
http://www.vet.osakafu-u.ac.jp/pham/
http://www.gelifesciences.co.jp/technologies/dharmacon/pdf/3795_dharmacon_accell_sirna_voc.pdf#search='%E4%B8%AD%E5%B6%8B%E7%A7%80%E6%BA%80'
http://www.vet.osakafu-u.ac.jp/pham/pham.html