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

FLORES MARTIN J; REYNA L; ROJAS ML; CRUZ DEL PUERTO MM

La Falda

Jornada; XXI Jornadas de la Sociedad de Biología de Córdoba; 2017

Sociedad de Biología de Córdoba

It is well-known that changes in the glucose concentration, lipidmetabolism and oxidative stress modulate the main cellularprocesses. Gestational diabetes leads to a lipotoxic placentalenvironment associated with increased inflammation andoxidative stress markers. Despite the fact that the majority ofglucose enters glycolysis, 25% of glucose can be metabolizedby HBP, which in turn leads to modification of variousintracellular proteins with O-linked GlcNAc. StarD7 belongs toSTART protein superfamily involved in lipid transport,metabolism and signaling. Here, we explored the influence ofelevated glucose levels (5.5 and 25 mM, previous starvation) onthe StarD7 expression in JEG-3 cells. Results showed an increasein StarD7 as well as in β-catenin expression following high-glucose treatment, and these effects were abolished by the HBPinhibitors, 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 glucosean induction in the Ire1 (2 and 24 h), GRP78 (2) proteins wasobserved. However, the phosphorylation of eIF2α at Ser 51decreased suggesting that OGlcNAc may regulate p-eIF2α. Instarvation conditions (0.5 mM glucose, without serum, during 16h) GRP78 and Ire1 levels were significantly elevated, whereasStarD7 decreased. Collectively, these results indicate that theinduction in StarD7 levels mediated by glucose leads by the HBPand also that glucose concentration changes induce activation ofthe UPR, providing evidence for a link between UPR and HBP.