Free fatty acids induce cell differentiation to infective forms in Trypanosoma cruzi.
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.
Wainszelbaum
Marisa J
MJ
Department of Microbiology, School of Medicine, University of Buenos Aires Paraguay 2155, 1121ABG Buenos Aires, Argentina.
Belaunzarán
María L
ML
Lammel
Estela M
EM
Florin-Christensen
Mónica
M
Florin-Christensen
Jorge
J
Isola
Elvira L D
EL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000493:pharmacokinetics / Q000494:pharmacology*; D007422:Intestines / Q000737:chemistry; D007546:Isoquinolines / Q000494:pharmacology; D019301:Oleic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014224:Triatoma / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007546:Isoquinolines; D013449:Sulfonamides; D019301:Oleic Acid; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate