High-NaCl induces SREBP-mediated transcriptional regulation of Triglycerides

WEBER, KAREN; CASALI, CECILIA IRENE; MALVICINI, RICARDO; PARRA LEANDRO; ETCHEVERRY TOMAS; FERNANDEZ TOME , MARIA DEL CARMEN

CORDOBA

Congreso; LII Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular- SAIB; 2016

SAIB

Hypertonicity regulates phospholipids (PLs) and TAG synthesis. These metabolic pathways can be regulated by transcriptionalactivation of their biosynthetic enzymes. Several transcription factors may be involved in such regulation but sterol response elementbinding protein (SREBP) is considered the master regulator of lipogenic genes. We showed that MDCK cells subjected to high NaClinduce changes in mRNA expression and cell distribution of SREBP isoforms. These changes were consistent with the increased levelsof PLs and TAG in treated cells and with the decrease in lipid synthesis after fatostatin treatment. However, we did not establish whichisoform, SREBP1 (S1) and/or SREBP2 (S2), is responsible for the increased lipogenic activity. The present work was aimed to addressthis. Before the addition of hypertonic medium, MDCK cells were treated with S1-siRNA, S2-siRNA or both. After NaCl treatmentlipid synthesis was studied. PLs and 1,2 DAG synthesis were not affected by any siRNA. In contrast, both 1,3 DAG and TAGsynthesis were blocked. S1-siRNA decreased DAG and TAG synthesis by 33 and 46 %. S2-siRNA decreased DAG and TAG by 40and 37%, respectively. Both siRNAs reduced synthesis by 55 %. So, SREBPs are needed to maintain TAG synthesis and itsdegradation to DAG but PLs synthesis remains constant indicating that SREBP-mediated transcriptional regulation is not involved