RGD Reference Report - Nuclear-translocated Glyceraldehyde-3-phosphate Dehydrogenase Promotes Poly(ADP-ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Nuclear-translocated Glyceraldehyde-3-phosphate Dehydrogenase Promotes Poly(ADP-ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke.

Authors: Nakajima, Hidemitsu  Kubo, Takeya  Ihara, Hideshi  Hikida, Takatoshi  Danjo, Teruko  Nakatsuji, Masatoshi  Shahani, Neelam  Itakura, Masanori  Ono, Yoko  Azuma, Yasu-Taka  Inui, Takashi  Kamiya, Atsushi  Sawa, Akira  Takeuchi, Tadayoshi 
Citation: Nakajima H, etal., J Biol Chem. 2015 Jun 5;290(23):14493-503. doi: 10.1074/jbc.M114.635607. Epub 2015 Apr 16.
RGD ID: 13792686
Pubmed: (View Article at PubMed) PMID:25882840
DOI: Full-text: DOI:10.1074/jbc.M114.635607

In addition to its role in DNA repair, nuclear poly(ADP-ribose) polymerase-1 (PARP-1) mediates brain damage when it is over-activated by oxidative/nitrosative stress. Nonetheless, it remains unclear how PARP-1 is activated in neuropathological contexts. Here we report that PARP-1 interacts with a pool of glyceradehyde-3-phosphate dehydrogenase (GAPDH) that translocates into the nucleus under oxidative/nitrosative stress both in vitro and in vivo. A well conserved amino acid at the N terminus of GAPDH determines its protein binding with PARP-1. Wild-type (WT) but not mutant GAPDH, that lacks the ability to bind PARP-1, can promote PARP-1 activation. Importantly, disrupting this interaction significantly diminishes PARP-1 overactivation and protects against both brain damage and neurological deficits induced by middle cerebral artery occlusion/reperfusion in a rat stroke model. Together, these findings suggest that nuclear GAPDH is a key regulator of PARP-1 activity, and its signaling underlies the pathology of oxidative/nitrosative stress-induced brain damage including stroke.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Gapdh  (glyceraldehyde-3-phosphate dehydrogenase)
Parp1  (poly (ADP-ribose) polymerase 1)

Genes (Mus musculus)
Gapdh  (glyceraldehyde-3-phosphate dehydrogenase)
Parp1  (poly (ADP-ribose) polymerase family, member 1)

Genes (Homo sapiens)
GAPDH  (glyceraldehyde-3-phosphate dehydrogenase)
PARP1  (poly(ADP-ribose) polymerase 1)


Additional Information