TY - JOUR
T1 - Modulation of calcium, neurotoxicity and arachidonic acid release by phospholipase a type II and glutamate in vitro
AU - Kolko, M.
AU - De Rodriguez Turco, E. B.
AU - Decoster, M. A.
AU - Bazan, N. G.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - Secretory phospholipase A Type II (sPLA2) may modulate neuronal function, under both physiological and pathological conditions. This 14 kDa enzyme, present in synaptic vesicles, is released by depolarization or neurotransmitter stimulation. Moreover, ischemia induces sPLA2 gene expression in rat brain. We evaluated the effect of sPLA2 from bee venom (BV) alone and with glutamate (GLU) on neurotoxicity through lactate dehydrogenase (LDH) release, intracellular free calcium concentration ([Co2+]i), and [3H] arachidonic acid (AA) release on primary cultures of cortical neurons. At 0.01 μml, BV was not toxic, did not affect basal oscillations in ([Co2+]i), but did induce [3H]AA release from phospholipids (PL). BV dose dependently (0.025-10 7mu;g/ml) caused neurotoxicity, altered [Ca2+]; dynamics, and stimulated [3H]AA release. GLU (80 μM) toxicity was similar to 0.5 μ g/ml BV (100% above control). Concentrations of BV (0.01 to 0.05 μ g/ml), which resulted in a 40-80% increase in LDH release when combined with GLU (80 μ M), elicited synergy in neurotoxocity (2.5-fold higher LDH release than their individual LDH values) and [3H]AA (1.5-fold). MK-801 blocked the synergy but not the BV effects. In contrast to the sustained [Co2+], response induced by GLU, BV dose-dependently (0.5-10 μ g/mL) induced a trancient increase in [Ca2+]i followed by decreased basal oscillations and a significant fall in [Ca2+]i. These results indicate that calcium-independent toxicity may occur at low sPtA2 concentrations and provide evidence for modulatory roles of sPLA2s in neuronal signal transduction.
AB - Secretory phospholipase A Type II (sPLA2) may modulate neuronal function, under both physiological and pathological conditions. This 14 kDa enzyme, present in synaptic vesicles, is released by depolarization or neurotransmitter stimulation. Moreover, ischemia induces sPLA2 gene expression in rat brain. We evaluated the effect of sPLA2 from bee venom (BV) alone and with glutamate (GLU) on neurotoxicity through lactate dehydrogenase (LDH) release, intracellular free calcium concentration ([Co2+]i), and [3H] arachidonic acid (AA) release on primary cultures of cortical neurons. At 0.01 μml, BV was not toxic, did not affect basal oscillations in ([Co2+]i), but did induce [3H]AA release from phospholipids (PL). BV dose dependently (0.025-10 7mu;g/ml) caused neurotoxicity, altered [Ca2+]; dynamics, and stimulated [3H]AA release. GLU (80 μM) toxicity was similar to 0.5 μ g/ml BV (100% above control). Concentrations of BV (0.01 to 0.05 μ g/ml), which resulted in a 40-80% increase in LDH release when combined with GLU (80 μ M), elicited synergy in neurotoxocity (2.5-fold higher LDH release than their individual LDH values) and [3H]AA (1.5-fold). MK-801 blocked the synergy but not the BV effects. In contrast to the sustained [Co2+], response induced by GLU, BV dose-dependently (0.5-10 μ g/mL) induced a trancient increase in [Ca2+]i followed by decreased basal oscillations and a significant fall in [Ca2+]i. These results indicate that calcium-independent toxicity may occur at low sPtA2 concentrations and provide evidence for modulatory roles of sPLA2s in neuronal signal transduction.
UR - http://www.scopus.com/inward/record.url?scp=33749111348&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:33749111348
SN - 0892-6638
VL - 10
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -