Flux through the hexosamine pathway is a determinant of nuclear factor kappaB- dependent promoter activation

Diabetes
Leighton R JamesJames W Scholey

Abstract

The hexosamine pathway may mediate some of the toxic effects of glucose. We hypothesized that flux through this pathway might regulate the activity of nuclear factor kappaB (NF-kappaB)-dependent genes in mesangial cells (MCs). In MCs, RT-PCR revealed that high glucose (30 mmol/l) and glucosamine (1 mmol/l) increased mRNA levels for vascular cell adhesion molecule 1 (VCAM-1) and increased the activity of an NF-kappaB enhancer by 1.5- and 2-fold, respectively. Overexpression of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme for flux through the hexosamine pathway, led to a 2.2-fold increase in NF-kappaB enhancer activity; the combination of GFAT overexpression and high glucose increased activity 2.8-fold, and these increases were prevented by 40 micromol/l O-diazoacetyl-L-serine (azaserine) or 6-diazo-5-oxonorleucine. High glucose, glucosamine, and GFAT overexpression increased binding of MC nuclear proteins to NF-kappaB consensus sequences. Immunoblotting revealed that the p65 subunit of NF-kappaB was O-glycosylated in MC cultured in physiologic glucose and that significant enhancement occurred with high glucose and glucosamine. Both glucose and glucosamine dose-dependently increased human VCAM-...Continue Reading

References

Dec 1, 1992·The Journal of Experimental Medicine·A S NeishT Collins
Nov 1, 1992·Journal of the American Society of Nephrology : JASN·D M BriscoeR S Cotran
Jan 17, 1995·Biochemical and Biophysical Research Communications·L M KhachigianJ W Fries
Jan 1, 1995·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·P MenèK H Thierauch
Nov 1, 1993·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·F N Ziyadeh
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·V CasolaroS J Ono
Mar 1, 1996·The American Journal of Physiology·M D RoosJ E Kudlow
Mar 1, 1997·Journal of the American Society of Nephrology : JASN·S J ShanklandJ W Scholey
May 1, 1997·Molecular and Cellular Biology·I Han, J E Kudlow
Oct 29, 1997·Molecular and Cellular Biology·M D RoosJ E Kudlow
Nov 18, 1997·Cell·I Stancovski, D Baltimore
Oct 14, 1998·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·V Lindner
Sep 3, 1999·Nature Biotechnology·W P Halford
Sep 17, 1999·The Journal of Biological Chemistry·M Karin
Dec 2, 1999·Biochimica Et Biophysica Acta·F I Comer, G W Hart
Feb 17, 2000·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·A B Fogo

❮ Previous
Next ❯

Citations

Oct 22, 2003·Current Opinion in Structural Biology·Chad Slawson, Gerald W Hart
Dec 18, 2010·Cell Death and Differentiation·P RamakrishnanD Baltimore
Nov 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Won Ho YangJin Won Cho
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Keiko KawauchiNobuyuki Tanaka
Apr 21, 2010·The Journal of Biological Chemistry·Stéphan HardivilléAnnick Pierce
May 16, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Luigi Gnudi
Nov 12, 2009·American Journal of Physiology. Endocrinology and Metabolism·Leighton R JamesJames W Scholey
Jan 31, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Natasha E Zachara
Dec 23, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Luyun ZouJohn C Chatham
Nov 26, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Boglarka LaczyJohn C Chatham
Aug 29, 2013·Science Signaling·Parameswaran RamakrishnanDavid Baltimore
Nov 24, 2011·Experimental Diabetes Research·Mi-Young KimYong Ho Ahn
Sep 3, 2013·Expert Review of Proteomics·Junfeng Ma, Gerald W Hart
Jan 14, 2016·International Urology and Nephrology·Ionel Alexandru ChecheriţăAdrian Covic
Dec 15, 2010·Pathology, Research and Practice·Leonidas D ArvanitisMarkos N Sgantzos
Nov 16, 2010·Diabetes & Metabolism·T IssadP Pagesy
Mar 6, 2010·Biochimica Et Biophysica Acta·Sabire OzcanJamie E L Cantrell
Apr 23, 2010·Journal of the American Society of Hypertension : JASH·Victor V LimaRita C Tostes
Oct 22, 2008·Trends in Endocrinology and Metabolism : TEM·Tarik Issad, Meishiue Kuo
May 8, 2007·Cellular Immunology·Ji-Biao HuangHoward R Petty
Feb 6, 2007·Gynécologie, obstétrique & fertilité·J LepercqS Hauguel de Mouzon
Jan 3, 2007·Animal Reproduction Science·Koji KimuraJeremy G Thompson
Sep 27, 2015·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Dongmei ZhangZhongwei Huang
Mar 3, 2009·The FEBS Journal·Carole Brasse-LagnelAnnie Husson
Oct 11, 2003·Biochemical and Biophysical Research Communications·G HeB Richelsen
Mar 5, 2003·Biochemical and Biophysical Research Communications·Lance WellsGerald W Hart
Jun 20, 2006·Biochimica Et Biophysica Acta·Natasha E Zachara, Gerald W Hart
Feb 24, 2006·Toxicology and Applied Pharmacology·Anabela P Rolo, Carlos M Palmeira
Apr 2, 2011·Biochemical and Biophysical Research Communications·In-Hyun Ryu, Su-Il Do
Oct 15, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Kitiporn PlaimasRainer König
Jul 11, 2012·The International Journal of Biochemistry & Cell Biology·Catia V DiogoMariusz R Wieckowski
Oct 26, 2013·The Biochemical Journal·Adam Ostrowski, Daan M F van Aalten
Sep 10, 2014·Biochemical and Biophysical Research Communications·Jamie ImbrioloM Faadiel Essop

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.