Modulation of phospholipase A2 activity in primary cultures of rat cortical neurons.
In neurons, phospholipase A2 (PLA2) plays a central role in the regulation of membrane phospholipid metabolism. We have addressed the pharmacological modulation of PLA2 in primary cultures of rat cortical neurons. Inhibition curves were obtained in 4 day-in-culture neurons treated for 30 minutes with either the dual PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), or the iPLA2 inhibitor bromoenol lactone (BEL). Full inhibition was achieved with 100 and 250 microM of MAFP, or 10 and 20 microM of BEL. Conversely, a dose-dependent activation of PLA2 was obtained with 10-20 microg/ml of melitin. PLA2 inhibition with MAFP or BEL was not acutely toxic for cultured neurons. However, sustained inhibition of the enzyme precluded the development of neurites, and resulted in long-term loss of neuronal viability. We present a model of pharmacological challenge of PLA2 in vitro, which can be further used to address the involvement of the enzyme in neurodevelopment and neurodegeneration models.
Mendes
C T
CT
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Brazil.
Gattaz
W F
WF
Schaeffer
E L
EL
Forlenza
O V
OV
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009281:Naphthalenes / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D063065:Organophosphonates / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D011247:Pregnancy; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000942:Antigens, Bacterial; D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D011753:Pyrones; C104810:methyl arachidonylfluorophosphonate; C043431:M antigen, Brucella melitensis; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A; D054467:Phospholipases A2