X-box binding protein 1 (XBP1): A key protein for renal osmotic adaptation. Its role in lipogenic program regulation

Publication date: Available online 9 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Cecilia Casali, Ricardo Malvicini, Luciana Erjavec, Leandro Parra, Ayelen Artuch, María C. Fernández TomeAbstractIn renal cells, hyperosmolarity can induce cellular stress or differentiation. Both processes require active endoplasmic reticulum (ER)-associated protein synthesis. Lipid biosynthesis also occurs at ER surface. We showed that hyperosmolarity upregulates glycerophospholipid (GP) and triacylglycerol (GL-TG) de novo synthesis. Considering that massive synthesis of proteins and/or lipids may drive to ER stress, herein we evaluated whether hyperosmolar environment induces ER stress and the participation of inositol-requiring enzyme 1α (IRE1α)-XBP1 in hyperosmotic-induced lipid synthesis. Treatment of Madin-Darby canine kidney (MDCK) cells with hyperosmolar medium triggered ER stress-associated unfolded protein response (UPR). Hyperosmolarity significantly increased xbp1 mRNA and protein as function of time; 24 h of treatment raised the spliced form of XBP1 protein (XBP1s) and induced its translocation to nuclear compartment where it can act as a transcription factor. XBP1 silencing or IRE1α ribonuclease (RNAse) inhibition impeded the expression of lipin1, lipin2 and diacylglycerol acyl transferase-1 (DGAT1) enzymes which yielded decreased GL-TG synthesis. The lack of XBP1s also decreased sterol regulatory element binding p...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research