Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE

Marie Paule Wautier, Olivier Chappey, Stefano Corda, David Stern, Ann Marie Schmidt, Jean Luc Wautier

Research output: Contribution to journalArticle

729 Citations (Scopus)

Abstract

Engagement of the receptor for advanced glycation end products (RAGE) by products of nonenzymatic glycation/oxidation triggers the generation of reactive oxygen species (ROS), thereby altering gene expression. Because dissection of the precise events by which ROS are generated via RAGE is relevant to the pathogenesis of complications in AGE-related disorders, such as diabetes and renal failure, we tested the hypothesis that activation of NADPH oxidase contributed, at least in part, to enhancing oxidant stress via RAGE. Here we show that incubation of human endothelial cells with AGEs on the surface of diabetic red blood cells, or specific AGEs, (carboxymethyl)lysine (CML)-modified adducts, prompted intracellular generation of hydrogen peroxide, cell surface expression of vascular cell adhesion molecule-1, and generation of tissue factor in a manner suppressed by treatment with diphenyliodonium, but not by inhibitors of nitric oxide. Consistent with an important role for NADPH oxidase, although macrophages derived from wild-type mice expressed enhanced levels of tissue factor upon stimulation with AGE, macrophages derived from mice deficient in a central subunit of NADPH oxidase, gp91phox, failed to display enhanced tissue factor in the presence of AGE. These findings underscore a central role of NADPH oxidase in AGE-RAGE-mediated generation of ROS and provide a mechanism for altered gene expression in AGE-related disorders.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume280
Issue number5 43-5
StatePublished - May 1 2001
Externally publishedYes

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NADPH Oxidase
Oxidants
Gene Expression
Thromboplastin
Reactive Oxygen Species
Macrophages
Vascular Cell Adhesion Molecule-1
Hydrogen Peroxide
Renal Insufficiency
Dissection
Nitric Oxide
Endothelial Cells
Erythrocytes
Advanced Glycosylation End Product-Specific Receptor

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. / Wautier, Marie Paule; Chappey, Olivier; Corda, Stefano; Stern, David; Schmidt, Ann Marie; Wautier, Jean Luc.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 280, No. 5 43-5, 01.05.2001.

Research output: Contribution to journalArticle

Wautier, Marie Paule ; Chappey, Olivier ; Corda, Stefano ; Stern, David ; Schmidt, Ann Marie ; Wautier, Jean Luc. / Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. In: American Journal of Physiology - Endocrinology and Metabolism. 2001 ; Vol. 280, No. 5 43-5.
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