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M9620872.TXT
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1996-02-26
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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).