Is SREBP involved in the hyperosmotic- upregulated lipid metabolism in renal cells?

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

Puerto Iguazú

Congreso; 56th International Conference on the Biochemistry of Lipids (ICBL).; 2015

ICBL

IS SREBP INVOLVED IN THE HYPEROSMOTIC- UPREGULATED LIPID METABOLISM IN RENAL CELLS? Weber K*, Casali CI*, Morel Gómez ED, Malvicini R, Fernández Tome MC.*Both are considered firth authorsMolecular and Cellular Biology, School of Pharmacy and Biochemistry, UBA. IQUIFIB-CONICET. Argentina. E-mail: karenweber@outlook.comRenal medullary cells are immersed in a hyperosmolar environment that contributes to the concentration of urine. In order to survive in such adverse conditions, cells develop adaptive and protective mechanisms. Previous works from our laboratory showed that phospholipid (PL) metabolism is essential for cell survival, as it preserves membrane structure and thus cell integrity and viability. We showed that changes in environmental osmolarity regulate PL synthesis that requires fatty acids which usually come from cellular storage in triglycerides (TAG) molecules. A key regulator of lipid metabolism is the sterol response element binding protein (SREBP), but to the present it has not been demonstrated its activation in response to changes in environmental osmolarity. Thus, the aim of this work was to evaluate TAG metabolism and the possible regulation through SREBP. For this purpose, MDCK cells were subjected to hyperosmolar medium (510±12 mOsm/kgH2O). TAG content and synthesis increased with hyperosmolarity, together with the expression of the main TAG biosynthetic enzymes, such as fatty acid synthase (FAS), acetyl-CoA carboxylase and lipin-2. Then, SREBP participation in this process was evaluated. SREBP protein and mRNA levels increased with hyperosmolarity. Also, translocation of SREBP to the nucleus was observed with hyperosmolar media. Fatostatin, a SREBP inhibitor, blocked hyperosmolar-increased TAG content and synthesis, and the expression of FAS enzyme. Finally, different signaling pathways involved in TAG synthesis and SREBP activation were evaluated, suggesting an important role of different phospholipases and MAPKs in this process.These results show that SREBP is activated in hyperosmolarity and suggest that this transcription factor modulates lipid synthesis. Thus, SREBP would play a key role in cell adaptation to osmotic changes by ensuring TAG synthesis that provides the substrates necessary for PL synthesis, leading to membrane homeostasis.Please indicate if Abstract competes for Oral Presentation: Yes ☐ No ☐