The role of oxidative stress and NF-κB activation in late diabetic complications

A common endpoint of hyperglycemia dependent cellular changes is the generation of reactive oxygen intermediates (ROIs) and the presence of elevated oxidative stress. Therefore, oxidative stress is supposed to play an important role in the development of late diabetic complications. Formation of adv...

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Bibliographische Detailangaben
Hauptverfasser: Abdel-Khalek, Mohamed (VerfasserIn) , Bierhaus, Angelika (VerfasserIn) , Schiekofer, Stephan (VerfasserIn) , Tritschler, Hans (VerfasserIn) , Ziegler, Reinhard (VerfasserIn) , Nawroth, Peter Paul (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1999
In: Biofactors
Year: 1999, Jahrgang: 10, Heft: 2/3, Pages: 157-167
ISSN:1872-8081
DOI:10.1002/biof.5520100211
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/biof.5520100211
Verlag, lizenzpflichtig, Volltext: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.5520100211
Volltext
Verfasserangaben:Abdel Khalek Mohamed, Angelika Bierhaus, Stephan Schiekofer, Hans Tritschler, Reinhard Ziegler and Peter P. Nawroth

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520 |a A common endpoint of hyperglycemia dependent cellular changes is the generation of reactive oxygen intermediates (ROIs) and the presence of elevated oxidative stress. Therefore, oxidative stress is supposed to play an important role in the development of late diabetic complications. Formation of advanced glycation end products (AGE's) due to elevated nonenzymatic glycation of proteins, lipids and nucleic acids is accompanied by oxidative, radical-generating reactions and thus represents a major source for oxygen free radicals under hyperglycemic conditions. Once formed, AGE's can influence cellular function by binding to several binding sites including the receptor for AGE's, RAGE. Binding of AGE's (and other ligands) to RAGE results in generation of intracellular oxidative stress and subsequent activation of the redox-sensitive transcription factor NF-κB in vitro and in vivo. Consistently, activation of NF-κB in diabetic patients correlates with the quality of glycemic control and can be reduced by treatment with the antioxidant α-lipoic acid. The development of techiques allowing for a tissue culture independent measurement of NF-κB activation in patients with diabetes mellitus gives insights into the molecular mechanisms linking diabetes mellitus and hyperglycemia with formation of advanced glycated endproducts and generation of oxidative stress finally resulting in oxidative stress mediated cellular activation. 
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