CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
HIGH GLUCOSE INDUCES STARD7 EXPRESSION IN JEG-3 TROPHOBLAST CELLS THROUGH THE HEXOSAMINE BIOSYNTHETIC PATHWAY (HBP)
Autor/es:
GENTI RAIMONDI S; ROJAS ML; PANZETTA DUTARI G; REYNA L; CRUZ DEL PUERTO M; FLORES MARTIN J
Lugar:
Córdoba
Reunión:
Congreso; XXI Jornadas científicas de la Sociedad de Biología de Córdoba; 2017
Institución organizadora:
Sociedad de Biología de Córdoba
Resumen:
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. Even though the majority of glucose enters glycolysis, ~ 2?5% of glucose can be metabolized by the hexosamine biosynthetic pathway (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 Ire1α (2 and 24 h) and GRP78 (2 h) proteins was observed. However, the phosphorylation of eIF2α at Ser 51 decreased suggesting that O-GlcNAc may regulate eIF2α phosphorylation. In starvation conditions (0.5 mM glucose, without serum, during 16 h) GRP78 and Ire1α levels were significantly elevated, whereas StarD7 decreased. Collectively, these results indicate that glucose induction of StarD7 levels is mediated by the HBP and, also, that changes in glucose concentration induce activation of the UPR, providing evidence for a link between UPR and HBP.