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

FLORES MARTIN J; REYNA L; CRUZ DEL PUERTO M; ROJAS ML; PANZETTA-DUTARI G; GENTI-RAIMONDI S

Paraná, Entre Ríos

Congreso; LIV Reunión Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2018

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

StarD7 is a lipid binding protein that transfer 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 modulates 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 whit 5.5 or 25 mM glucose at 2, 4 and 24 h (compare with 0,5mM glucose) and the protein levels 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 Ire1 levels were significantly elevated, whereas StarD7 and β-catenin 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, whereas no changes were observed 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.