6533b825fe1ef96bd128285f
RESEARCH PRODUCT
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.
Osamu NishioRenate KlöckingHiroshi UshijimaWerner E.g. MüllerSanja Perovicsubject
Agonistmedicine.drug_classNeurotoxinsPharmacologyHIV Envelope Protein gp120Receptors N-Methyl-D-Aspartatechemistry.chemical_compoundPhospholipase A2medicineAnimalsFragmentation (cell biology)Rats WistarCytotoxicityCells CulturedNeuronsArachidonic AcidbiologyCell DeathGeneral NeuroscienceNeurotoxicitymedicine.diseaseRatsnervous systemchemistryCell cultureQuinacrinebiology.proteinHIV-1NMDA receptorArachidonic acidDNA Damagedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1995-06-01 | The European journal of neuroscience |