Molecular Biology Reports

, Volume 45, Issue 6, pp 2593–2600 | Cite as

Hexosamine pathway regulates StarD7 expression in JEG-3 cells

  • Jésica Flores-Martín
  • Luciana Reyna
  • Mariano Cruz Del Puerto
  • María L. Rojas
  • Graciela M. Panzetta-Dutari
  • Susana Genti-RaimondiEmail author
Original Article


StarD7 is a lipid binding protein involved in the delivery of phosphatidylcholine to the mitochondria whose promoter is activated by Wnt/β-catenin signaling. Although the majority of glucose enters glycolysis, ~ 2–5% of it can be metabolized via the hexosamine biosynthetic pathway (HBP). Considering that HBP has been implicated in the regulation of β-catenin we explored if changes in glucose levels modulate StarD7 expression by the HBP in trophoblast cells. We found an increase in StarD7 as well as in β-catenin expression following high-glucose (25 mM) treatment in JEG-3 cells; these effects were abolished in the presence of HBP inhibitors. Moreover, since HBP is able to promote unfolded protein response (UPR) the protein levels of GRP78, Ire1α, calnexin, p-eIF2α and total eIF2α as well as XBP1 mRNA was measured. Our results indicate that a diminution in glucose concentration leads to a decrease in StarD7 expression and an increase in the UPR markers: GRP78 and Ire1α. Conversely, an increase in glucose is associated to high StarD7 levels and low GRP78 expression, phospho-eIF2α and XBP1 splicing, although Ire1α remains high when cells are restored to high glucose. Taken together these findings indicate that glucose modulates StarD7 and β-catenin expression through the HBP associated to UPR, suggesting the existence of a link between UPR and HBP in trophoblast cells. This is the first study reporting the effects of glucose on StarD7 in trophoblast cells. These data highlight the importance to explore the role of StarD7 in placenta disorders related to nutrient availability.


Hexosamine pathway StarD7 START domain JEG-3 cells UPR 







Eukaryotic translation initiation factor 2 subunit 1α


Endoplasmic reticulum


Fetal bovine serum


Glutamine fructose-6-phosphate amidotransferase




Glucose regulated protein 78


Hexosamine biosynthetic pathway


Inositol-requiring enzyme 1




O-GlcNAc transferase


Small interfering RNA


StAR-related lipid transfer (START) domain containing 7


Tris buffered saline


Uridine diphosphate N-acetylglucosamine


Unfolding protein response.



This work was funded by the Agencia Nacional de Promoción Ciencia y Técnica (FONCYT) PICT 2014-0806 and 2015-1781, and the Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECyT-UNC). S.G-R. and G.M.P-D. are Career Investigators of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). J F-M, L-R, M-CDP and ML-R thank FONCYT and CONICET for her fellowships.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Departamento de Bioquímica Clínica, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina
  2. 2.Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)CórdobaArgentina
  3. 3.Departamento de Bioquímica Clínica, CIBICI-CONICET, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina

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