Hexosamine biosynthetic pathway (HBP) regulates StarD7 expression in JEG-3 cells

JÉSICA FLORES-MARTIN; LUCIANA REYNA; MARIANO CURZ DEL PUERTO; MARÍA LAURA ROJAS; GRACIELA PANZETTA DE DUTARI; SUSANA GENTI DE RAIMONDI

Paraná

Congreso; LIV Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2018

StarD7 is a lipid binding protein that transfers phosphatidylcholine to the mitochondria. Our studies indicated that StarD7 protein levels are important to maintain JEG-3 trophoblast cellular homeostasis. It is well-known that changes in lipid metabolism and glucose concentration modulate several physiological processes. Moreover, glucose flux through the HBP leads to modification of various intracellular proteins with O-linked GlcNAc. Here, we explored the influence of elevated glucose levels on the StarD7 expression in JEG-3 cells. Results showed an increase in StarD7 as well as β-catenin expression when cells were incubated with 5.5 or 25 mM glucose at 2, 4, or 24 h (compared with 0.5 mM glucose) and these effects were reduced by the HBP inhibitors: azaserine and 6-Diazo-5-oxo-L-norleucine. In addition, the main markers of unfolded protein response (UPR) were assessed. In starvation conditions (0.5 mM glucose, over night) GRP78 and Ire1α levels were significantly elevated, whereas StarD7 and β-catenin were decreased. When cells were incubated with high glucose concentration, an early induction of GRP78 levels was observed, decreasing at 24 h. Related to Ire1α protein, a significant increased expression was detected with no changes in calnexin protein expression. The phosphorylation of eIF2α at Ser 51 decreased at all time assayed. These results indicate that glucose modulates StarD7 levels through HBP and also, that changes in glucose concentration induce activation of the UPR in trophoblast cells.