Effect of tamoxifen on the sphingolipid biosynthetic pathway in the different intraerythrocytic stages of the apicomplexa Plasmodium falciparum.

T. A. PIÑERO; M. LANDONI; V. G. DUSCHAK; A. M. KATZIN; A. S. COUTO

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2018

0006-291X

Parasites of the genus Plasmodium responsible for Malaria are obligate intracellular pathogens residing inmammalian red blood cells, hepatocytes, or mosquito midgut epithelial cells. Regarding that detailedknowledge on the sphingolipid biosynthetic pathway of the apicomplexan protozoan parasites is scarce,different stages of Plasmodium falciparum were treated with tamoxifen in order to evaluate the effects ofthis drug on the glycosphingolipid biosynthesis. Thin layer chromatography, High performance reversephase chromatography and UV-MALDI-TOF mass spectrometry were the tools used for the analysis. Inthe ring forms, the increase of NBD-phosphatidyl inositol biosynthesis was notorious but differences atNBD-GlcCer levels were undetectable. In trophozoite forms, an abrupt decrease of NBD-acylatedGlcDHCer and NBD-GlcDHCer in addition to an increase of NBD-PC biosynthesis was observed. On thecontrary, in schizonts, tamoxifen seems not to be producing substantial changes in lipid biosynthesis. Ourfindings indicate that in this parasite, tamoxifen is exerting an inhibitory action on Glucosylcer-amidesynthase and sphingomyelin synthase levels. Moreover, regarding that Plasmodium does not bio-synthesize inositolphosphoceramides, the accumulation of phosphatidylinositol should indicate aninhibitory action on glycosylinositol phospholipid synthesis.