Intestinal extracts of Triatoma infestans induce cell differentiation of Trypanosoma cruzi epimastigotes into the infective metacyclic form. Part of this effect can be explained by the presence of haemoglobin fragments, which stimulate trypanosomal adenylate cyclase. In this work we examined the metacyclogenic activity of lipids present in this intestinal extract. We found that lipid extracts of the intestinal extract have significant stimulatory effects that reside with the free-fatty-acid fraction, especially oleic acid. These compounds stimulate de novo diacylglycerol formation and protein kinase C activity in the parasite. Moreover, metacyclogenesis is stimulated by phorbol esters and cell-permeant diacylglycerol, while protein kinase C down-regulation or incubation with inhibitors of this kinase abrogates this effect. These results indicate that free fatty acids are a novel signal, inducing metacyclogenesis, acting through a pathway involving diacylglycerol biosynthesis and protein kinase C activation.
Abbreviations used: DG, diacylglycerol; dibutyryl-cAMP, N6,2′-O-dibutyryladenosine 3′,5′-cyclic monophosphate sodium salt; FFA, free fatty acids; HA1004, N-(2-guanidioenthyl)-5-isoquinolinesulphonamide; H7, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine; OA, oleic acid; OAG, 1-oleoyl 2-acetyl-sn-glycerol; PC, phosphatidylcholine; PKA, protein kinase A; PKC, protein kinase C.