Suppression of Pyk2 attenuated the increased tyrosine phosphorylation of NMDA receptor subunit 2A after brain ischemia in rat hippocampus

Neurosci Lett. 2005 Apr 29;379(1):55-8. doi: 10.1016/j.neulet.2004.12.054. Epub 2005 Jan 12.

Abstract

Effects of suppressing the protein expression of Pyk2 on increased tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunit 2A (NR2A) after brain ischemia in rat hippocampus were studied with immunoprecipitation and immunoblot. Transient (15 min) brain ischemia and reperfusion (I/R) was induced by four-vessel occlusion in Sprague-Dawley (SD) rats. I/R led to increases of tyrosine phosphorylation of NR2A and interaction of Pyk2 and Src kinase with NR2A after 6 h of reperfusion. The increases were attenuated by Pyk2 antisense oligonucleotides intracerebroventricularly infused every 24 h for 4 days before ischemia, but not missense oligonucleotides or vehicle. The antisense also inhibited the increased auto-phosphorylation of Pyk2 and Src kinase, while the protein expression of NR2A or Src kinase had no obvious change under the above conditions. The data suggested that Pyk2 may be involved in facilitating NR2A tyrosine phosphorylation by Src kinase after I/R.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Brain Ischemia / metabolism*
  • Disease Models, Animal
  • Focal Adhesion Kinase 2
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Immunoprecipitation / methods
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Tyrosine / metabolism*
  • src-Family Kinases / metabolism

Substances

  • Oligodeoxyribonucleotides, Antisense
  • Receptors, N-Methyl-D-Aspartate
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 2
  • Ptk2b protein, rat
  • src-Family Kinases
  • N-methyl D-aspartate receptor subtype 2A