HIGH GLUCOSE INDUCES STARD7 EXPRESSION IN JEG-3 TROPHOBLAST CELLS THROUGH THE HEXOSAMINE BIOSYNHETIC PATHWAY (HBP)

LA FALDA-CORDOBA

Jornada; XXI JORNADAS CIENTIFICAS Sociedad de Biología de Córdoba; 2017

SOCIEDAD DE BIOLOGÍA DE CÓRDOBA

It is well-known that changes in the glucose concentration, lipid metabolism and oxidative stress modulate the main cellular processes. Gestational diabetes leads to a lipotoxic placental environment associated with increased inflammation and oxidative stress markers. Despite the fact that the majority of glucose enters glycolysis, ~ 2?5% of glucose can be metabolized by HBP, which in turn leads to modification of various intracellular proteins with O-linked GlcNAc. StarD7 belongs to START protein superfamily involved in lipid transport, metabolism and signaling. Here, we explored the influence of elevated glucose levels (5.5 and 25 mM, previous starvation) on the StarD7 expression in JEG-3 cells. Results showed an increase in StarD7 as well as in β-catenin expression following high-glucose treatment, and these effects were abolished by the HBP inhibitors, azaserine and 6-Diazo-5-oxo-L-norleucine. In addition, the levels of the main markers of unfolded protein response (UPR) were assessed. When cells were moved to 5.5 or 25 mM glucose an induction in the Ire1 (2 and 24 h), GRP78 (2) proteins was observed. However, the phosphorylation of eIF2α at Ser 51 decreased suggesting that OGlcNAc may regulate p-eIF2α. In starvation conditions (0.5 mM glucose, without serum, during 16 h) GRP78 and Ire1 levels were significantly elevated, whereas StarD7 decreased. Collectively, these results indicate that the induction in StarD7 levels mediated by glucose leads by the HBP and also that glucose concentration changes induce activation of the UPR, providing evidence for a link between UPR and HBP.