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Competitive binding of postsynaptic density 95 and Ca2+-calmodulin dependent protein kinase II to N-methyl-D-aspartate receptor subunit 2B in rat brain.

AbstractAIM:
To investigate the interactions among postsynaptic density 95 (PSD-95), Ca2+-calmodulin dependent protein kinase IIalpha (CaMKIIalpha), and N-methyl-D-aspartate receptor subunit 2B (NR2B) during ischemia and reperfusion in hippocampus of rats.
METHODS:
Brain ischemia was induced by four-vessel occlusion procedure in rats. Immunoprecipitation and immunoblotting were performed to study the interactions and phosphorylation of proteins. The association-dissociation of PSD-95 and CaMKIIalpha to and from N-methyl-D-aspartate (NMDA) receptor induced by ischemia and reperfusion and the effects of 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-piperazine (KN-62, a selective inhibitor of CaMKII) on these protein interactions were investigated. Coimmunoprecipitation and immunoblotting were performed for the studies of interactions among proteins.
RESULTS:
The alternations of the binding level of PSD-95 and CaMKIIalpha to NR2B during ischemia and reperfusion demonstrated the negative correlation to each other. Pre-administration of KN62 through both cerebral ventricles inhibited the 10 min ischemia-induced increase of the binding of PSD-95 to NR2B and, on the contrary, promoted the binding of CaMKIIalpha to NR2B.
CONCLUSION:
PSD-95 competes with CaMKII to bind to NR2B during ischemia and reperfusion in rat hippocampus.
AuthorsFan-jie Meng, Jun Guo, Bo Song, Xue-bo Yan, Guang-yi Zhang
JournalActa pharmacologica Sinica (Acta Pharmacol Sin) Vol. 25 Issue 2 Pg. 176-80 (Feb 2004) ISSN: 1671-4083 [Print] United States
PMID14769205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • postsynaptic density proteins
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Camk2a protein, rat
Topics
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology)
  • Animals
  • Binding, Competitive
  • Brain Ischemia (complications)
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
  • Disks Large Homolog 4 Protein
  • Hippocampus (metabolism)
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins
  • Nerve Tissue Proteins (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate (metabolism)
  • Reperfusion Injury (etiology, metabolism)

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