       Document 0872
 DOCN  M9620872
 TI    Exposure to gp120 of HIV-1 induces an increased release of arachidonic
       acid in rat primary neuronal cell culture followed by NMDA
       receptor-mediated neurotoxicity.
 DT    9602
 AU    Ushijima H; Nishio O; Klocking R; Perovic S; Muller WE; Institute of
       Public Health, Tokyo, Japan.
 SO    Eur J Neurosci. 1995 Jun 1;7(6):1353-9. Unique Identifier : AIDSLINE
       MED/96073244
 AB    After incubation of highly enriched neurons from rat cerebral cortex
       with the HIV-1 coat protein gp120 for 18 h, cells showed fragmentation
       of DNA at internucleosomal linkers followed by NMDA receptor-mediated
       neurotoxicity. We report that in response to exposure to gp120 cells
       react with an increased release of arachidonic acid (AA) via activation
       of phospholipase A2. This process was not inhibited by NMDA receptor
       antagonists. To investigate the role of AA on the sensitivity of the
       NMDA receptor towards its agonist, low concentrations of NMDA were
       co-administered with AA. This condition enhanced the NMDA-mediated
       cytotoxicity. Administration of mepacrine reduced cytotoxicity caused by
       gp120. We conclude that gp120 causes an activation of phospholipase A2,
       resulting in the increased release of AA, which may in turn sensitize
       the NMDA receptor.
 DE    Animal  Arachidonic Acid/ANTAGONISTS & INHIB/*METABOLISM  Cell Death
       Cells, Cultured  DNA Damage/DRUG EFFECTS  HIV Envelope Protein
       gp120/*PHARMACOLOGY  *HIV-1  Neurons/*DRUG
       EFFECTS/*METABOLISM/PHYSIOLOGY  Neurotoxins/*PHARMACOLOGY
       Quinacrine/PHARMACOLOGY  Rats  Rats, Wistar  Receptors,
       N-Methyl-D-Aspartate/ANTAGONISTS & INHIB/*PHYSIOLOGY  Support, Non-U.S.
       Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

