Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures.
Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (</=100 ng/ml), induced a decrease of [3H]arachidonate-phospholipids and preferential reesterification of the fatty acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations, below those exerting highest toxicity. Synergy in neurotoxicity and [3H]arachidonate release was observed when low, nontoxic (10 ng/ml, 0.71 nM), or mildly toxic (25 ng/ml, 1. 78 nM) concentrations of sPLA2 were added together with glutamate (80 microM). A similar synergy was observed with the sPLA2 OS2, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role for this enzyme in the modulation of glutamatergic synaptic function and of excitotoxicity.
Kolko
M
M
LSU Neuroscience Center and Department of Ophthalmology, Louisiana State University Medical Center, School of Medicine, New Orleans, Louisiana 70112, USA. nbazan@lsumc.edu
DeCoster
M A
MA
de Turco
E B
EB
Bazan
N G
NG
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001514:Bee Venoms / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D005971:Glutamates / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010741:Phospholipases A / Q000378:metabolism / Q000633:toxicity*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D001514:Bee Venoms; D005971:Glutamates; D009498:Neurotoxins; D010743:Phospholipids; D016718:Arachidonic Acid; D016291:Dizocilpine Maleate; D010741:Phospholipases A; D054467:Phospholipases A2