Targeted disruption of PSD-93 gene reduces platelet-activating factor-induced neurotoxicity in cultured cortical neurons

Yun Xu, Bosheng Zhang, Zichun Hua, Roger A. Johns, David S. Bredt, Yuan Xiang Tao

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

PSD-93, a molecular adaptive protein, binds to and clusters the N-methyl-D-aspartate (NMDA) receptor and assembles a specific set of signaling proteins (for example neuronal nitric oxide synthase, nNOS) around the NMDA receptor at synapses in the central nervous system. This suggests that PSD-93 might mediate many NMDA receptor-dependent physiological and pathophysiological functions. We report here that PSD-93 colocalizes and interacts with the NMDA receptor and neuronal nitric oxide synthase in cultured cortical neurons. Targeted disruption of PSD-93 gene significantly prevented NMDA receptor-nitric oxide signaling-dependent neurotoxicity triggered via platelet-activating factor (PAF) receptor activation. In addition, the deficiency of PSD-93 markedly attenuated platelet-activating factor-induced increase in cyclic guanosine 3′,5′-monophosphate (cGMP) and prevented platelet-activating factor-promoted formation of NMDA receptor-neuronal nitric oxide synthase complex. These findings indicate that PSD-93 is involved in the NMDA receptor-nitric oxide-mediated pathological processing of neuronal damage triggered via platelet-activating factor receptor activation. Since platelet-activating factor is a potent neuronal injury mediator during the development of brain trauma, seizures, and ischemia, the present work suggests that PSD-93 might contribute to molecular mechanisms of neuronal damage in these brain disorders.

Original languageEnglish (US)
Pages (from-to)16-24
Number of pages9
JournalExperimental Neurology
Volume189
Issue number1
DOIs
StatePublished - Sep 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Keywords

  • Cell culture
  • N-methyl-D-aspartate receptor
  • Neurotoxicity
  • PSD-93
  • Platelet-activating factor

Fingerprint Dive into the research topics of 'Targeted disruption of PSD-93 gene reduces platelet-activating factor-induced neurotoxicity in cultured cortical neurons'. Together they form a unique fingerprint.

Cite this