The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB
Abstract
Activation of the transcription factor nuclear factor-κB (NF-κB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-κB in vitro, we observed a long-lasting sustained activation of NF-κB in the absence of decreased IκBα in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-κBp65. A comparable increase in NF-κBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-β peptide (Aβ) to the transmembrane receptor for AGE (RAGE) results in protein synthesis–dependent sustained activation of NF-κB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a β-globin reporter transgene under control of NF-κB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-κB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-κB activation by ligands of RAGE was mediated by initial degradation of IκB proteins followed by new synthesis of NF-κBp65 mRNA and protein in the presence of newly synthesized IκBα and IκBβ. These data demonstrate that ligands of RAGE can induce sustained activation of NF-κB as a result of increased levels of de novo synthesized NF-κBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-κB activation observed in hyperglycemia and possibly other chronic diseases.
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Function and Activation of NF-kappaB in the Immune System
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Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
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RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
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Self-citationBlockade of RAGE-amphoterin signalling suppresses tumour growth and metastases
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Self-citationLander, H. M., Tauras, J. M., Ogiste, J. S., Hori, O., Moss, R. A., & Schmidt, A. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.28.17810 · Cited by 813
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Self-citationProtective genes expressed in endothelial cells: a regulatory response to injury
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Cited by
The concept of allostasis in biology and biomedicine
McEwen, B. S., & Wingfield, J. C. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00024-7 · Cited by 3,302
Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890
Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury
Goldin, A., Beckman, J. A., Schmidt, A. M., & Creager, M. A. (2006) · Circulation · doi:10.1161/circulationaha.106.621854 · Cited by 2,261
Self-citationMcEwen, B. S., & Gianaros, P. J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05331.x · Cited by 1,715
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2003) · Diabetes · doi:10.2337/diabetes.52.1.1 · Cited by 1,482
Metadata
- Authors
- Bierhaus, A., Schiekofer, S., Schwaninger, M., Andrassy, M., Humpert, P. M., Chen, J., Hong, M., Luther, T., Henle, T., Klöting, I., Morcos, M., Hofmann, M., Tritschler, H., Weigle, B., Kasper, M., Smith, M., Perry, G., Schmidt, A.-M., Stern, D. M., Häring, H.-U., Schleicher, E., & Nawroth, P. P.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-12-01
- Volume
- 50
- Issue
- 12
- Pages
- 2792-2808
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2013730613
- Cited by
- 824
- References
- 10
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bierhaus, A., Schiekofer, S., Schwaninger, M., Andrassy, M., Humpert, P. M., Chen, J., Hong, M., Luther, T., Henle, T., Klöting, I., Morcos, M., Hofmann, M., Tritschler, H., Weigle, B., Kasper, M., Smith, M., Perry, G., Schmidt, A.-M., Stern, D. M., . . . Nawroth, P. P. (2001). Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB. Diabetes. https://doi.org/10.2337/diabetes.50.12.2792
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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