title: Knock-down of postsynaptic density protein 95 expression by antisense oligonucleotides protects against apoptosis-like cell death induced by oxygen-glucose deprivation in vitro.
abstract: OBJECTIVE
  Postsynaptic density protein 95 (PSD-95) plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors (NMDARs). In this study, the functional roles of PSD-95 in tyrosine phosphorylation of NMDAR subunit 2A (NR2A) and in apoptosis-like cell death induced by oxygen-glucose deprivation (OGD) in cultured rat cortical neurons were investigated.
  
  
  METHODS
  We used immunoprecipitation and immunoblotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining.
  
  
  RESULTS
  Tyrosine phosphorylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucleotides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition.
  
  
  CONCLUSIONS
  PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis-like cell death after recovery from OGD.
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Yan
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zong
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D055785:Gene Knockdown Techniques / Q000379:methods; D005947:Glucose / Q000378:metabolism; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D005947:Glucose; D010100:Oxygen