Possible role of sphingosine 1p (s1p) as a survival factor in mdck cells submitted to hypertonic stress

PESCIO L, LEOCATA F, FERNÁNDEZ TOME M, STERIN-SPEZIALE N.

Pinamar, Argentina

Congreso; 10 th Congreso of Panamerican Association for Biochemistry and Molecular Biology (PABMB) and XLI Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular- SAIB; 2005

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

BIOCELL 29 (Suppl.), 2005 LP-P9. POSSIBLE ROLE OF SPHINGOSINE 1P (S1P) AS A SURVIVAL FACTOR IN MDCK CELLS SUBMITTED TO HYPERTONIC STRESS Pescio L, Leocata F, Fernández Tome M, Sterin-Speziale N. Biología Celular. Facultad de Farmacia y Bioquímica, UBA. IQUIFIB-CONICET. Buenos Aires, ARGENTINA. E-mail: speziale@ffyb.uba.ar Renal papilla is the kidney zone that performs the final adjustment of urine composition. Structurally is constituted by tubular collecting ducts which have to survive and function in a non-favorable environment since are submitted to the highest renal interstitial tonicity. Sphingolipids constitute a lipid family with diverse relevant physiological actions such as constituting biomembranes (Sphingomyelin, SM), inducing cell differentiation (ceramide, Cer) or proliferation and survival (sphingosine 1P, S1P). In order to determine the contribution of these molecules to cell survival in hypertonic conditions, we studied sphingolipid metabolism in renal epithelial cells submitted to high NaCl concentration. Confluentarrested MDCK cultures were grown in physiological or hypertonic media (150 or 250 mM NaCl, respectively) for 24 and 48 hs and 32P-Pi and 14C-palmitic acid (P), which monitors de novo synthesis, incorporation to SM, Cer and S1P was determined. Hypertonicity increased S1P de novo synthesis by 58 and 46%, while induced a slight increase (26%) or a decrease (39%) in 14C-P incorporation to Cer after 24 and 48 hs, respectively. No changes were observed in radioactive SM after 24hs but after 48 hs of hypertonicity, SM labeling increased by 40% (14C) and 92% (32P) respectively. Considering that hypertonicity caused a dramatic drop in cell number, showing the remaining cells high viability, the above results suggest that cell survives to changes in media tonicity by inducing the synthesis of survival molecules such as S1P and dowregulating Cer production. P-Pi and 14C-palmitic acid (P), which monitors de novo synthesis, incorporation to SM, Cer and S1P was determined. Hypertonicity increased S1P de novo synthesis by 58 and 46%, while induced a slight increase (26%) or a decrease (39%) in 14C-P incorporation to Cer after 24 and 48 hs, respectively. No changes were observed in radioactive SM after 24hs but after 48 hs of hypertonicity, SM labeling increased by 40% (14C) and 92% (32P) respectively. Considering that hypertonicity caused a dramatic drop in cell number, showing the remaining cells high viability, the above results suggest that cell survives to changes in media tonicity by inducing the synthesis of survival molecules such as S1P and dowregulating Cer production. 14C-P incorporation to Cer after 24 and 48 hs, respectively. No changes were observed in radioactive SM after 24hs but after 48 hs of hypertonicity, SM labeling increased by 40% (14C) and 92% (32P) respectively. Considering that hypertonicity caused a dramatic drop in cell number, showing the remaining cells high viability, the above results suggest that cell survives to changes in media tonicity by inducing the synthesis of survival molecules such as S1P and dowregulating Cer production. 14C) and 92% (32P) respectively. Considering that hypertonicity caused a dramatic drop in cell number, showing the remaining cells high viability, the above results suggest that cell survives to changes in media tonicity by inducing the synthesis of survival molecules such as S1P and dowregulating Cer production.