A phospholipase A(2) isolated from Lachesis muta snake venom increases the survival of retinal ganglion cells in vitro

作者：da Silva Cunha Karinne Cristinne; Fuly Andre Lopes^*; de Araujo Elizabeth Giestal

来源：Toxicon, 2011, 57(4): 580-585.

DOI：10.1016/j.toxicon.2010.12.021

• Lysophosphatidylcholine
• Phospholipase A(2)
• Lachesis muta
• Snake venom
• Retinal ganglion cell

We have previously showed that a phospholipase A(2) isolated from Lachesis muta snake venom and named LM-PLA(2)-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-PLA(2)-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-PLA(2)-I increased the survival of ganglion cells (100% when compared to control cultures) and the treatment of LM-PLA(2)-I with p-bromophenacyl bromide abolished this effect. This result indicates that the effect of LM-PLA(2)-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-PLA(2)-I upon ganglion cell survival. To investigate the mechanism of action of LM-PLA(2)-I, cultures were treated with chelerythrine chloride, BAFTA-AM, rottlerin and also with an inhibitor of c-junc kinase (JNKi). Our results showed that rottlerin and JNK inhibitor abolished the LM-PLA(2)-I on ganglion cell survival. Taken together, our results showed that LM-PLA(2)-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 PLA(2) enzyme and LPC in controlling the survival of axotomized neuronal cells.

• 出版日期2011-3-15