Sphingolipid metabolism is a sharp regulator of a renal epithelial cell proliferation

UDOVIN LD; FAVALE NO; STERIN SPEZIALE NB

Ciudad de Buenos Aires

Congreso; XLIX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2013

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Sphingosine Kinase (SK) is a key regulator enzyme in lipidic metabolism that regulates the balance between sphingosine and sphingosine-1-Phosphate (S1P), being S1P a lipid involved in several cellular processes. We have demonstrated that SK is strongly expressed in renal epithelial cells and is a key regulator in cell survival. In the present work we evaluate the importance of the tight regulation of SK activity in renal epithelial cell cycle. For this purpose, MDCK cells cultured at low density were seeded with 10% BFS for 24 hs, to allow cell cycle progression. Then, cell were treated or not with D,L-threo-dihydrosphingosine (DHS), a selective SK1 inhibitor at different concentrations( 1,5 and 1,75µM). SK inhibition induced a decrease in cell number in a concentration dependent manner after 24 hs of incubation (257,200, 129,650 and 85,768 cells, control, 1.5 and 1.75 µM respectively) with no alteration in cell viability. Cells were arrested in G1 phase (57.9%, 72.7% and 76.1% for Control, 1.5 and 1.75 µM, respectively) and decreased of mitotic cell/field (4.5, 1.4 and 1.3 for Control, 1.5 and 1.75 µM, respectively) showing a cell cycle arrest. In summary we proposed that depending on SK rate activity, the enzyme can be, not only a regulator of the cell survival, but also of the cell cycle progression