Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins

Shi Du Yan, Ann Marie Schmidt, G. Mark Anderson, Jinghua Zhang, Jerold Brett, Yu Shan Zou, David Pinsky, David Stern

Research output: Contribution to journalArticle

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Abstract

Attack by reactive oxygen intermediates, common to many kinds of cell/tissue injury, has been implicated in the development of diabetic and other vascular diseases. Such oxygen-free radicals can be generated by advanced glycation end products (AGEs), which are nonenzymatically glycated and oxidized proteins. Since cellular interactions of AGEs are mediated by specific cellular binding proteins, receptor for AGE (RAGE) and the lactoferrin-like polypeptide (LF-L), we tested the hypothesis that AGE ligands tethered to the complex of RAGE and LF-L could induce oxidant stress. AGE albumin or AGEs immunoisolated from diabetic plasma resulted in induction of endothelial cell (EC) oxidant stress, including the generation of thiobarbituric acid reactive substances (TBARS) and resulted in the activation of NF-κB, each of which was blocked by antibodies to AGE albumin into normal animals led to the appearance of malondialdehyde determinants in the vessel wall and increased TBARS in the tissues, activation of NF-κB, and induction of heme oxygenase mRNA. AGE-induced oxidant stress was inhibited by pretreatment of animals with either antibodies to the AGE receptor/binding proteins or antioxidants. These data indicate that interaction of AGEs with cellular targets, such as ECs, leads to oxidant stress resulting in changes in gene expression and other cellular properties, potentially contributing to the development of vascular lesions. Further studies will be required to dissect whether oxidant stress occurs on the cell surface or at an intracellular locus.

Original languageEnglish (US)
Pages (from-to)9889-9897
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number13
StatePublished - Apr 1 1994
Externally publishedYes

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Advanced Glycosylation End Products
Oxidants
Carrier Proteins
Thiobarbituric Acid Reactive Substances
Albumins
Animals
Chemical activation
Tissue
Oxygen
Heme Oxygenase (Decyclizing)
Diabetic Angiopathies
Peptides
Lactoferrin
Antibodies
Endothelial cells
Malondialdehyde
Gene expression
Free Radicals
Blood Vessels
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. / Yan, Shi Du; Schmidt, Ann Marie; Anderson, G. Mark; Zhang, Jinghua; Brett, Jerold; Zou, Yu Shan; Pinsky, David; Stern, David.

In: Journal of Biological Chemistry, Vol. 269, No. 13, 01.04.1994, p. 9889-9897.

Research output: Contribution to journalArticle

Yan, SD, Schmidt, AM, Anderson, GM, Zhang, J, Brett, J, Zou, YS, Pinsky, D & Stern, D 1994, 'Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins', Journal of Biological Chemistry, vol. 269, no. 13, pp. 9889-9897.
Yan, Shi Du ; Schmidt, Ann Marie ; Anderson, G. Mark ; Zhang, Jinghua ; Brett, Jerold ; Zou, Yu Shan ; Pinsky, David ; Stern, David. / Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 13. pp. 9889-9897.
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