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Int. J. Mol. Sci. 2013, 14(10), 19891-19910; doi:10.3390/ijms141019891
Review

Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

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Received: 8 August 2013; in revised form: 5 September 2013 / Accepted: 5 September 2013 / Published: 1 October 2013
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Abstract: Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.
Keywords: receptor for advanced glycation endproduct; non-enzymatic glycation; inflammation; redox signaling receptor for advanced glycation endproduct; non-enzymatic glycation; inflammation; redox signaling
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Daffu, G.; del Pozo, C.H.; O'Shea, K.M.; Ananthakrishnan, R.; Ramasamy, R.; Schmidt, A.M. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond. Int. J. Mol. Sci. 2013, 14, 19891-19910.

AMA Style

Daffu G, del Pozo CH, O'Shea KM, Ananthakrishnan R, Ramasamy R, Schmidt AM. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond. International Journal of Molecular Sciences. 2013; 14(10):19891-19910.

Chicago/Turabian Style

Daffu, Gurdip; del Pozo, Carmen H.; O'Shea, Karen M.; Ananthakrishnan, Radha; Ramasamy, Ravichandran; Schmidt, Ann M. 2013. "Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond." Int. J. Mol. Sci. 14, no. 10: 19891-19910.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert