Sphingomyelin synthase1 activity is implicated in mdck cells epithelial- mesenchymal transition

FAVALE NICOLAS; SANTACREU BRUNO; MARÍA GABRIELA MÁRQUEZ; STERIN-SPEZIALE NORMA B

Mendoza

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIONES BIOQUÍMICAS Y DE BIOLOGÍA MOLECULAR (SAIB); 2012

SOCIEDAD ARGENTINA DE INVESTIGACIONES BIOQUÍMICAS Y DE BIOLOGÍA MOLECULAR (SAIB)

We have demonstrated that sphingomyelin (SM) biosynthesis is essential for hypertonicity-induced MDCK cell differentiation. Under inhibition of SM synthesis, MDCK cells instead of differentiate switch to mesenchymal phenotype, thus performing an epithelial to mesenchymal transition (EMT). We aim to study the sphingolipid metabolic pathway as well as the sphingomyelin synthase isoform 1 (SMS1) involvement in such process. MDCK cells were subjected to hypertonicity and concomitantly treated or not (control) with 15 μM D609 (SMS inhibitor) or siRNA-SMS1. Sphingolipid metabolism was determined by using radioactive precursors in the presence or absence of cicloserine (CS) or Fumonisin B1 (FB1). By using D609 as well as siRNA SMS1 the characteristic polarized phenotype of the cells was lost and it was not retrieved by a concomitant treatment with CS or FB1; suggesting no intermediates accumulation participation. Acquirement of mesenchymal phenotype was accompanied by alterations in amount and localization of the epithelial markers (ECadh, Cad16 and ZO-1) and mesenchymal markerVimentin. These results demonstrate implication of SM synthesis in the EMT. Is important to note thatEMThas been implicated in the development of cancer and renal fibrosis, consequently SMS1 activity emerges as a possible target molecule for the study of such important human pathologies.