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SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines

SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose,...

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Autores principales: Wex, Brigitte, Safi, Rémi M., Antonios, Gregory, Zgheib, Perla Z., Awad, Dania B., Kobeissy, Firas H., Mahfouz, Rami A., El-Sabban, Marwan M., Yazbek, Soha N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100323/
https://www.ncbi.nlm.nih.gov/pubmed/29867058
http://dx.doi.org/10.3390/molecules23061350
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author Wex, Brigitte
Safi, Rémi M.
Antonios, Gregory
Zgheib, Perla Z.
Awad, Dania B.
Kobeissy, Firas H.
Mahfouz, Rami A.
El-Sabban, Marwan M.
Yazbek, Soha N.
author_facet Wex, Brigitte
Safi, Rémi M.
Antonios, Gregory
Zgheib, Perla Z.
Awad, Dania B.
Kobeissy, Firas H.
Mahfouz, Rami A.
El-Sabban, Marwan M.
Yazbek, Soha N.
author_sort Wex, Brigitte
collection PubMed
description SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and localization were assayed using Western blot and immunostaining. Localization was confirmed using a proximity ligation assay. Two-dimensional (2D) gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35B4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35B4 in the Golgi apparatus suggests its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1) and linked to the pathogenesis of diabetes or post-translationally modified by O-GlcNAc. Glucose levels activate SLC35B4 expression. This triggers a downstream effect via Hsp60 and other proteins. We hypothesize that the downstream effect on the proteins is mediated via altering the glycosylation pattern inside liver cells. The downstream cascade ultimately alters the ability of cultured liver cells to inhibit endogenous glucose production, and this could play a role in the association of the above-listed genes with the pathogenesis of diabetes.
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spelling pubmed-61003232018-11-13 SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines Wex, Brigitte Safi, Rémi M. Antonios, Gregory Zgheib, Perla Z. Awad, Dania B. Kobeissy, Firas H. Mahfouz, Rami A. El-Sabban, Marwan M. Yazbek, Soha N. Molecules Article SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and localization were assayed using Western blot and immunostaining. Localization was confirmed using a proximity ligation assay. Two-dimensional (2D) gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35B4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35B4 in the Golgi apparatus suggests its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1) and linked to the pathogenesis of diabetes or post-translationally modified by O-GlcNAc. Glucose levels activate SLC35B4 expression. This triggers a downstream effect via Hsp60 and other proteins. We hypothesize that the downstream effect on the proteins is mediated via altering the glycosylation pattern inside liver cells. The downstream cascade ultimately alters the ability of cultured liver cells to inhibit endogenous glucose production, and this could play a role in the association of the above-listed genes with the pathogenesis of diabetes. MDPI 2018-06-04 /pmc/articles/PMC6100323/ /pubmed/29867058 http://dx.doi.org/10.3390/molecules23061350 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wex, Brigitte
Safi, Rémi M.
Antonios, Gregory
Zgheib, Perla Z.
Awad, Dania B.
Kobeissy, Firas H.
Mahfouz, Rami A.
El-Sabban, Marwan M.
Yazbek, Soha N.
SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title_full SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title_fullStr SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title_full_unstemmed SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title_short SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines
title_sort slc35b4, an inhibitor of gluconeogenesis, responds to glucose stimulation and downregulates hsp60 among other proteins in hepg2 liver cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100323/
https://www.ncbi.nlm.nih.gov/pubmed/29867058
http://dx.doi.org/10.3390/molecules23061350
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