Lysophosphatidylcholine produced by the phospholipase A2 isolated from Lachesis muta snake venom modulates natural killer activity as a protein kinase C effector.
We have showed that a phospholipase A(2) isolated from Lachesis muta snake venom, denoted LM-PLA(2)-I, had some biological effects. Here, we examined its effects on lymphocytes. Pre-incubation of human peripheral blood lymphocytes with LM-PLA(2)-I plus phosphatidylcholine (PC) stimulated the natural killer (NK) activity. This was accompanied by DNA binding of nuclear transcription factor kappaB and the increase in PKC activity with translocation of the enzyme from the cytoplasma into the plasma membrane. These effects were reproduced when lymphocytes were pre-incubated with commercial lysophosphatidylcholine (LPC) and abolished by stausrosporin or p-bromophenacyl bromide. Evaluation of phosphorylated PKC isoforms showed that pre-incubation with LPC activated the autophosphorylation of the PKCzeta isoform. Taken together, these results confirm that the enzymatic activity of the phospholipase A(2) present in L. muta venom is for the biological activity of the snake venom, and strongly suggest that the LPC produced may be acting as a modulator of PKC isoforms.
Fuly
André L
AL
Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho s/n, Niterói, Rio de Janeiro 24210-150, Brazil. andfuly@vm.uff.br
Machado
Alexandre L
AL
Castro
Paulo
P
Abrahão
Agessandro
A
Redner
Paulo
P
Lopes
Ulisses G
UG
Guimarães
Jorge A
JA
Koatz
Vera Lucia G
VL
D000818:Animals; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000737:chemistry* / Q000201:enzymology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D017819:Viperidae / Q000378:metabolism
D003435:Crotalid Venoms; C072644:Lachesis venom; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D020033:Protein Isoforms; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D019311:Staurosporine