SK1 As Key G1-G0 Transition Modulator In Renal Epithelial Cell

UDOVIN LD; SANTACREU BJ; STERIN-SPEZIALE NB; FAVALE NO

Mar del Plata, Buenos Aires

Congreso; LI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2015

SAIB

Sphingosine Kinase (SK) is a key enzyme involved in the synthesis of sphingosine-1-Phosphate (S1P), a lipid mediator that regulates several cellular processes. S1P has been characterized as a dual signaling molecule with the ability to activate different effectors. We demonstrated that S1P biosynthesis present a gradual decrease during kidney maturation and cell proliferation. In this report we evaluate the SK activity in renal epithelial cell cycle modulation and in the transit to cell differentiation For this, MDCK cells were cultured at low density to allow cell cycle progression and were treated with D,L-threo-dihydrosphingosine (tDHS), a SK1 inhibitor. SK inhibition induced a decrease in cell number after 24 h of incubation with no alteration in cell viability. Besides, treatment for 24 h with tDHS caused cell cycle arrest in G0/G1 phase with cyclin D1 accumulation. Cell cycle arrest was accompanied with hypophosphorilation of Rb protein. These results suggest that intracellular S1P was involved in cell cycle arrest. Moreover, SK inhibition induced an increase in the percentage of cell in G0 phase after tDHS treatment accompanied by cellular morphological changes. These suggest that S1P is not only involved in cell cycle arrest (with induction of cell quiescence), but also participates in cell differentiation.