Exposure of proteins to reducing sugars results in nonenzymatic glycation with the ultimate formation of advanced glycation end products (AGEs). One means through which AGEs modulate cellular functions is through binding to specific cell surface acceptor molecules. The receptor for AGEs (RAGE) is such a receptor and is a newly identified member of the immunoglobulin superfamily expressed on endothelial cells (ECs), mononuclear phagocytes (MPs), and vascular smooth muscle cells (SMCs) in both vivo and in vitro. Binding of AGEs to RAGE results in induction of cellular oxidant stress, as exemplified by the generation of thiobarbituric acid-reactive substances, expression of heme oxygenase type I, and activation of the transcription factor NF-kB, with consequences for a range of cellular functions. AGEs on the surface of diabetic red cells enhance binding to endothelial RAGE and result in enhanced oxidant stress in the vessel wall. By using reagents to selectively block access to RAGE, the role of this receptor in AGE-mediated perturbation of cellular properties can be dissected in detail.
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GLYCATION, OXIDATIVE STRESS, AND SCAVENGER ACTIVITY|
July 01 1996
Rage: A Novel Cellular Receptor for Advanced Glycation End Products
Ann Marie Schmidt;
Ann Marie Schmidt
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Osamu Hori;
Osamu Hori
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Rong Cao;
Rong Cao
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Shi Du Yan;
Shi Du Yan
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Jerold Brett;
Jerold Brett
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Jean-Luc Wautier;
Jean-Luc Wautier
Laboratoire de Recherche en Biologie Vasculaire et Cellulaire, Unite d'Immunohematologie, Hopital Lariboisiere, Universie Paris 7
Faculte de Medecine, Paris, France
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Satoshi Ogawa;
Satoshi Ogawa
First Department of Medicine, Osaka University School of Medicine
Osaka, Japan
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Keisuke Kuwabara;
Keisuke Kuwabara
First Department of Medicine, Osaka University School of Medicine
Osaka, Japan
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Masayasu Matsumoto;
Masayasu Matsumoto
First Department of Medicine, Osaka University School of Medicine
Osaka, Japan
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David Stern
David Stern
Departments of Medicine, Physiology and Surgery, Columbia University, College of Physicians and Surgeons
New York, New York
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Address correspondence and reprint requests to Dr. Ann Marie Schmidt, Department of Physiology, P&S 11–518, Columbia University, College of Physicians and Surgeons, 630 W. 168th St., New York, NY 10032
Citation
Ann Marie Schmidt, Osamu Hori, Rong Cao, Shi Du Yan, Jerold Brett, Jean-Luc Wautier, Satoshi Ogawa, Keisuke Kuwabara, Masayasu Matsumoto, David Stern; Rage: A Novel Cellular Receptor for Advanced Glycation End Products. Diabetes 1 July 1996; 45 (Supplement_3): S77–S80. https://doi.org/10.2337/diab.45.3.S77
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