title: 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.
abstract: 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.
authors.affiliation: Institute of Public Health, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ushijima
authors.forename: O
authors.initials: O
authors.lastname: Nishio
authors.forename: R
authors.initials: R
authors.lastname: Klöcking
authors.forename: S
authors.initials: S
authors.lastname: Perovic
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016923:Cell Death; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D015699:HIV Envelope Protein gp120; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D016718:Arachidonic Acid; D011796:Quinacrine