High NaCl differentially regulates PL and TAG homeostasis in renal cells.

WEBER, KAREN; CASALI, CECILIA IRENE; MALVICINI, RICARDO; GOMEZ MOREL, EMANUEL; FERNANDEZ TOME, MARIA DEL CARMEN

Rosario, Santa Fe

Congreso; L Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular; 2014

Renal papillary cells are surrounded by the highest osmolarities of the body due to their function in concentrating urine. In order to survive in these adverse conditions, they must have protective mechanisms. We previously showed that this kidney zone has the highest synthesis and phospholipid (PL) turnover, and that this helps to preserve membrane structure and cell viability. Fatty acids, necessary for PL synthesis, are stored as triacylglicerols (TAG) in lipid droplets. We showed that hyperosmolarity increased TAG content and synthesis in MDCK cells. In this work we evaluate which signaling pathway mediates hyperosmolarity-regulated lipid metabolism. MDCK were subjected to hyperosmolality (298-512 mOsm/kg H2O) for 48h, treated with different phospholipases (PLA2, PLD, PLC-PI and PLC-PC) or kinases (PI3K, PKC or MAPKs) inhibitors and labeled using [14C]-Glycerol. After treatments, lipids were extracted, separated by TLC and quantified. PLC-PI and PLC-PC inhibitors increased PL and TAG synthesis, whereas cPLA2 and iPLA2 inhibitors prevented hyperosmotic-induced lipid synthesis. PLD activity was only involved in PL homeostasis. MAPKs inhibitors did not affect PL and TAG synthesis. PKC and PI3K were mediating TAG, but not PL, synthesis. These data show that hyperosmolarity differentially regulates PL and TAG homeostasis in renal cells.