A phospholipase A2 isolated from Lachesis muta snake venom increases the survival of retinal ganglion cells in vitro

摘要

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.