The role of XBP-1 in osmotic activated-lipid synthesis

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

Cordoba

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

SAIB

It is known that hypertonicity induces an abrupt synthesis of several osmoprotective proteins such as urea transporters, COX2, AQP2,AQP3, among others, and organic osmolytes. It is also known that a massive protein synthesis could cause endoplasmic reticulum(ER) stress. Previously, we showed that hypertonicity activates the expression of ER stress markers in MDCK cells subjected to highNaCl concentrations, XBP-1 and CHOP, among them. The active form of XBP-1 is a transcription factor that activates the expressionof lipogenic genes which, in turn, activate membrane biogenesis and ER stress alleviation. As hypertonicity significantly increaseslipid synthesis in renal cells, in the present work we evaluated whether XBP-1 is involved in such response. To do that, prior tohypertonicity treatment, MDCK cultures were treated with XBP1siRNA. After 24 h of hypertonic treatment, the synthesis of lipids andthe expression of key lipogenic enzymes were assayed. NaCl treatment, significantly increased the synthesis of both phospholipids(PL) and triglycerides (TAG); XBP1 silencing reduced the levels 1,2 DAG and TAG formed. This finding was consistent with thedecrease in the levels of Lipin2 and DGAT2 mRNA. Interestingly, PL synthesis was not affected. These results clearly evidence amajor role of XBP1 in the regulation of lipid synthesis in renal epithelial cells.*Both last authors.