PMID- 22958338
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121107
LR  - 20211021
IS  - 1750-2187 (Electronic)
IS  - 1750-2187 (Linking)
VI  - 7
IP  - 1
DP  - 2012 Sep 8
TI  - NADPH oxidase mediates the oxygen-glucose deprivation/reperfusion-induced 
      increase in the tyrosine phosphorylation of the N-methyl-D-aspartate receptor 
      NR2A subunit in retinoic acid differentiated SH-SY5Y Cells.
PG  - 15
LID - 10.1186/1750-2187-7-15 [doi]
AB  - BACKGROUND: Evidence exists that oxidative stress promotes the tyrosine 
      phosphorylation of N-methyl-D-aspartate receptor (NMDAR) subunits during 
      post-ischemic reperfusion of brain tissue. Increased tyrosine phosphorylation of 
      NMDAR NR2A subunits has been reported to potentiate receptor function and 
      exacerbate NMDAR-induced excitotoxicity. Though the effect of ischemia on 
      tyrosine phosphorylation of NMDAR subunits has been well documented, the 
      oxidative stress signaling cascades mediating the enhanced tyrosine 
      phosphorylation of NR2A subunits remain unclear. RESULTS: We report that the 
      reactive oxygen species (ROS) generator NADPH oxidase mediates an oxidative 
      stress-signaling cascade involved in the increased tyrosine phosphorylation of 
      the NR2A subunit in post-ischemic differentiated SH-SY5Y neuroblastoma cells. 
      Inhibition of NADPH oxidase attenuated the increased tyrosine phosphorylation of 
      the NMDAR NR2A subunit, while inhibition of ROS production from mitochondrial or 
      xanthine oxidase sources failed to dampen the post-ischemic increase in tyrosine 
      phosphorylation of the NR2A subunit. Additionally, inhibition of NADPH oxidase 
      blunted the interaction of activated Src Family Kinases (SFKs) with PSD-95 
      induced by ischemia/reperfusion. Lastly, inhibition of NADPH oxidase also 
      markedly reduced cell death in post-ischemic SH-SY5Y cells stimulated by NMDA. 
      CONCLUSIONS: These data indicate that NADPH oxidase has a key role in 
      facilitating NMDAR NR2A tyrosine phosphorylation via SFK activation during 
      post-ischemic reperfusion.
FAU - Beske, Phillip H
AU  - Beske PH
AD  - From the Department of Biomedical and Pharmaceutical Sciences and the Center for 
      Structural and Functional Neuroscience, The University of Montana, Missoula, MT, 
      59812, USA. Darrell.Jackson@mso.umt.edu.
FAU - Jackson, Darrell A
AU  - Jackson DA
LA  - eng
PT  - Journal Article
DEP - 20120908
PL  - England
TA  - J Mol Signal
JT  - Journal of molecular signaling
JID - 101271526
PMC - PMC3489596
EDAT- 2012/09/11 06:00
MHDA- 2012/09/11 06:01
PMCR- 2012/09/08
CRDT- 2012/09/11 06:00
PHST- 2012/07/30 00:00 [received]
PHST- 2012/09/04 00:00 [accepted]
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2012/09/11 06:01 [medline]
PHST- 2012/09/08 00:00 [pmc-release]
AID - 1750-2187-7-15 [pii]
AID - 10.1186/1750-2187-7-15 [doi]
PST - epublish
SO  - J Mol Signal. 2012 Sep 8;7(1):15. doi: 10.1186/1750-2187-7-15.