title: A phospholipase A₂ isolated from Lachesis muta snake venom increases the survival of retinal ganglion cells in vitro.
abstract: We have previously showed that a phospholipase A₂ isolated from Lachesis muta snake venom and named LM-PLA₂-I displayed particular biological activities, as hemolysis, inhibition on platelet aggregation, edema induction and myotoxicity. In the present work, we evaluated the effect of LM-PLA₂-I on the survival of axotomized rat retinal ganglion cells kept in vitro, as well as its mechanism of action. Our results clearly showed that treatment with LM-PLA₂-I increased the survival of ganglion cells (100% when compared to control cultures) and the treatment of LM-PLA₂-I with p-bromophenacyl bromide abolished this effect. This result indicates that the effect of LM-PLA₂-I on ganglion cell survival is entirely dependent on its enzymatic activity and the generation of lysophosphatidylcholine (LPC) may be a prerequisite to the observed survival. In fact, commercial LPC mimicked the effect of LM-PLA₂-I upon ganglion cell survival. To investigate the mechanism of action of LM-PLA₂-I, cultures were treated with chelerythrine chloride, BAPTA-AM, rottlerin and also with an inhibitor of c-junc kinase (JNKi). Our results showed that rottlerin and JNK inhibitor abolished the LM-PLA₂-I on ganglion cell survival. Taken together, our results showed that LM-PLA₂-I and its enzymatic product, LPC promoted survival of retinal ganglion cells through the protein kinase C pathway and strongly suggest a possible role of the PLA₂ enzyme and LPC in controlling the survival of axotomized neuronal cells.
authors.affiliation: Programa de Pós-Graduação em Neurociências, Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Karinne Cristinne
authors.initials: KC
authors.lastname: da Silva Cunha
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Fuly
authors.forename: Elizabeth Giestal
authors.initials: EG
authors.lastname: de Araujo
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000201:enzymology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2 / Q000494:pharmacology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: C489138:1,3-benzothiazol-2-yl(2-((2-(3-pyridinyl)ethyl)amino)-4-pyrimidinyl)acetonitrile; D000097:Acetonitriles; D000098:Acetophenones; D053119:Benzophenanthridines; D001578:Benzopyrans; D052160:Benzothiazoles; D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; C072644:Lachesis venom; D008244:Lysophosphatidylcholines; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C085746:rottlerin; C016299:chelerythrine; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide