Wnt-b-catenin signaling and high glucose levels regulate StarD7 expression

RENA VIVIANA; ANGELETTI SOFÍA; CAMOLOTTO SOLEDAD; PANZETTA-DUTARI GRACIELA; GENTI-RAIMONDI SUSANA

Mar del Plata. Argentina

Congreso; XLIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

StarD7 belongs to the START domain proteins involved in intracellular transport and lipid metabolism. To understand the molecular mechanisms that regulate the StarD7 expression, we characterized the 5´ region of the gene. We reported that StarD7 promoter is activated by SF-1 and this effect is increased by cAMP. Here we demonstrate that an additional regulatory element corresponding to TCF-4 binding site appears important for StarD7 expression, since a reporter gene expression is reduced when this site is deleted, implicating Wnt/b-catenin signaling. Co-transfection assays in JEG-3 and COS-7 cell demonstrated that StarD7 promoter is activated by b-catenin S33Y. Since this activation implies the inactivation of GSK-3b and a glucose storage diminution, we study whether glucose level modify StarD7 expression. A significantly increased StarD7 mRNA, determined by quantitative real time PCR, was found in JEG-3 and HepG2 cells cultured in high glucose compared to the cells cultured in low glucose medium. Also, both StarD7 mRNA and a reporter gene driven by StarD7 promoter were up-regulated by inhibition of GSK-3b. Furthermore, the transcript levels of a list of factors involved in transcriptional control of glucose and lipid metabolism were evaluated. These studies provide novel insights into the regulation of StarD7 gene by Wnt-b-catenin signaling associated to glucose and lipid metabolism. [Supported by CONICET, FONCyT and SECyT-UNC].