Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Portero-Otín, M.
Right arrow Articles by Nègre-Salvayre, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Portero-Otín, M.
Right arrow Articles by Nègre-Salvayre, A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 51:1535-1542, 2002
© 2002 by the American Diabetes Association, Inc.

Advanced Glycation End Product Precursors Impair Epidermal Growth Factor Receptor Signaling

Manuel Portero-Otín1, Reinald Pamplona1, Maria Josep Bellmunt1, Maria Cristina Ruiz1, Joan Prat1, Robert Salvayre2, and Anne Nègre-Salvayre2

1 Metabolic Pathophysiology Research Group, Department of Basic Medical Sciences, University of Lleida, Lleida, Spain
2 Institut National de Santé et de Recherche Médicale (INSERM) U466 and Biochemistry Department, Centre Hospitalier Universitaire Rangueil, University Paul Sabatier, Toulouse, France

Formation of advanced glycation end products (AGEs) is considered a potential link between hyperglycemia and chronic diabetic complications, including disturbances in cell signaling. It was hypothesized that AGEs alter cell signaling by interfering with growth factor receptors. Therefore, we studied the effects of two AGE precursors, glyoxal (GO) and methylglyoxal (MGO), on the epidermal growth factor receptor (EGFR) signaling pathway in cultured cells. Both compounds prevented tyrosine autophosphorylation induced by epidermal growth factor (EGF) in a time- and dose-dependent manner as well as phospholipase C{gamma}1 recruitment and subsequent activation of extracellular signal-regulated kinases. AGE precursors inhibit EGF-induced EGFR autophosphorylation and tyrosine kinase activity in cell membranes and in EGFR immunoprecipitates. In addition, AGE precursors strongly inhibited cellular phosphotyrosine phosphatase activities and residual EGFR dephosphorylation. AGE precursors induced the formation of EGFR cross-links, as shown by the cross-reactivity of modified EGFR with an anti-N{epsilon}(carboxymethyl)lysine antibody, suggesting that altered EGFR signaling was related to carbonyl-amine reactions on EGFR. Aminoguanidine, an inhibitor of AGE formation, partially prevented the EGFR dysfunction induced by GO and MGO. These data introduce a novel mechanism for impaired cellular homeostasis in situations that lead to increased production of these reactive aldehydes, such as diabetes.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
A.-V. Cantero, M. Portero-Otin, V. Ayala, N. Auge, M. Sanson, M. Elbaz, J.-C. Thiers, R. Pamplona, R. Salvayre, and A. Negre-Salvayre
Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-{beta}: implications for diabetic atherosclerosis
FASEB J, October 1, 2007; 21(12): 3096 - 3106.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
X. Jia, D. J. H. Olson, A. R. S. Ross, and L. Wu
Structural and functional changes in human insulin induced by methylglyoxal
FASEB J, July 1, 2006; 20(9): 1555 - 1557.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Riboulet-Chavey, A. Pierron, I. Durand, J. Murdaca, J. Giudicelli, and E. Van Obberghen
Methylglyoxal impairs the insulin signaling pathways independently of the formation of intracellular reactive oxygen species.
Diabetes, May 1, 2006; 55(5): 1289 - 1299.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M Alves, D A. Cunha, V C. Calegari, M J A Saad, A C. Boschero, L A. Velloso, and E M. Rocha
Nuclear factor-{kappa}B and advanced glycation end-products expression in lacrimal glands of aging rats
J. Endocrinol., October 1, 2005; 187(1): 159 - 166.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
H.-J. Luth, V. Ogunlade, B. Kuhla, R. Kientsch-Engel, P. Stahl, J. Webster, T. Arendt, and G. Munch
Age- and Stage-dependent Accumulation of Advanced Glycation End Products in Intracellular Deposits in Normal and Alzheimer's Disease Brains
Cereb Cortex, February 1, 2005; 15(2): 211 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
A. J.M. Boulton, R. A. Malik, J. C. Arezzo, and J. M. Sosenko
Diabetic Somatic Neuropathies
Diabetes Care, June 1, 2004; 27(6): 1458 - 1486.
[Full Text] [PDF]

Home page
 DiabetesHome page
M. Peppa, H. Brem, P. Ehrlich, J.-G. Zhang, W. Cai, Z. Li, A. Croitoru, S. Thung, and H. Vlassara
Adverse Effects of Dietary Glycotoxins on Wound Healing in Genetically Diabetic Mice
Diabetes, November 1, 2003; 52(11): 2805 - 2813.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Speer, S. Morkunaite-Haimi, J. Liobikas, M. Franck, L. Hensbo, M. D. Linder, P. K. J. Kinnunen, T. Wallimann, and O. Eriksson
Rapid Suppression of Mitochondrial Permeability Transition by Methylglyoxal: ROLE OF REVERSIBLE ARGININE MODIFICATION
J. Biol. Chem., September 12, 2003; 278(37): 34757 - 34763.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2002 by the American Diabetes Association.