Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

TY - JOUR

T1 - Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

AU - Kolko, M

AU - DeCoster, M A

AU - de Turco, E B

AU - Bazan, N G

AU - Kolko, Miriam

PY - 1996/12/20

Y1 - 1996/12/20

N2 - 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.

AB - 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.

KW - Animals

KW - Arachidonic Acid

KW - Bee Venoms

KW - Cell Death

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Dizocilpine Maleate

KW - Drug Synergism

KW - Glutamates

KW - Neurons

KW - Neurotoxins

KW - Phospholipases A

KW - Phospholipases A2

KW - Phospholipids

KW - Rats

M3 - Journal article

C2 - 8955105

SN - 0021-9258

VL - 271

SP - 32722

EP - 32728

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

IS - 51

ER -