Protein kinase C is involved in metacyclogenesis of Trypanosoma cruzi.

BELAUNZARÁN ML, WAINSZELBAUM MJ, ALOISE MM, GIMENEZ G, FLORIN-CHRISTENSEN J, ISOLA ELD.

Villa Carlos Paz, Córdoba

Otro; XXXVIII Reunión de la Sociedad Argentina de Bioquímica y Biología Molecular.; 2002

Sociedad Argentina de Bioquímica y Biología Molecular

We have shown that phorbol esters and cell-permeant diacylglycerols induce metacyclogenesis of T.cruzi epimastigotes. Moreover, metacyclogenic effects of Triatoma infestans intestinal extracts are substantially abrogated by protein kinase C (PKC) inhibitors, including HA 1004 and Bisindolylmaleimide. Here, we studied protein phosphorylation induced by the intestinal extracts and diacylglycerol oleoyl-acyl-glycerol (OAG). We found that both agents induce similar phosphorylation patterns with bands of Mr 180, 120 and 26 characteristically labeled. These bands are also phosphorylated by exposure to 300 mM oleic acid, a lipid that induces diacylglycerol biosynthesis and is metacyclogenic. A markedly different pattern was induced by 1 mM Dibutyryl cAMP, which results in labeling of a band of approx. 38 kDa, that is not found in cells exposed with intestinal extracts. We found that PKC down-regulation by long term treatment with phorbol esters abrogates the metacyclogenic effects of the intestinal extracts. We conclude that PKC stimulation plays a key role in metacyclogenesis of T.cruzi, and that the free fatty acids of the intestinal extract can account at least partially for this effect. Further, we suggest that stimulation of the PKC pathways prevent activation of PKA, which thus appears as an alternative differentiation route