Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G

M. T. Corasaniti, M. C. Strongoli, S. Piccirilli, R. Nisticò, A. Costa, A. Bilotta, P. Turano, A. Finazzi-Agrò, G. Bagetta

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of a single dose of the HIV-1 coat protein gp120 given into one lateral cerebral ventricle (i.c.v.) on the expression of cyclooxygenase type 2 (COX-2) and PGE2 levels have been studied using Western blotring and ELISA techniques applied to brain tissue extracts obtained from the neocortex of individual rats, one of the regions of the central nervous system where the viral protein causes apoptosis. The results demonstrate that COX-2 expression is almost doubled 6 h after a single dose (100 ng) of gp120 and this is paralleled by a statistically significant elevation of PGE2. Enhanced COX-2 expression is implicated in the mechanisms of apoptosis evoked by gp120 because the latter is prevented by NS398 (10 mg/kg i.p.), a selective inhibitor of COX-2 activity. Protection is also afforded by NMDA receptor antagonists, such as MK801 (0.3 mg/kg i.p.) and CGP040116 (10 mg/kg i.p.), and by the free radical scavenger, U-74389G (10 mg/kg i.p.), supporting a glutamate-mediated, excitotoxic, mechanism of apoptotic death induced by gp120. These data together with the observation that MK801 failed to prevent gp120-enhanced COX-2 expression indicate that products of the arachidonic cascade may be responsible for elevation of synaptic glutamate leading neocortical cells to oxidative stress and excitotoxic apoptosis. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)664-669
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume274
Issue number3
DOIs
Publication statusPublished - Aug 11 2000

Keywords

  • Apoptosis
  • COX-2
  • HIV-1 gp120
  • NMDA receptor antagonists
  • Prostaglandins
  • U-74389G

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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