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Superoxide Dismutases: Role in Redox Signaling, Vascular Function and Diseases

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Title: Superoxide Dismutases: Role in Redox Signaling, Vascular Function and Diseases
Author(s): Fukai, Tohru; Ushio-Fukai, Masuko
Subject(s): Superoxide Dismutases cardiovascular
Abstract: Excessive reactive oxygen species Revised abstract, especially superoxide anion (O2•−), play important roles in the pathogenesis of many cardiovascular diseases, including hypertension and atherosclerosis. Superoxide dismutases (SODs) are the major antioxidant defense systems against O2•−, which consist of three isoforms of SOD in mammals: the cytoplasmic Cu/ZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3), all of which require catalytic metal (Cu or Mn) for their activation. Recent evidence suggests that in each subcellular location, SODs catalyze the conversion of O2•− H2O2, which may participate in cell signaling. In addition, SODs play a critical role in inhibiting oxidative inactivation of nitric oxide, thereby preventing peroxynitrite formation and endothelial and mitochondrial dysfunction. The importance of each SOD isoform is further illustrated by studies from the use of genetically altered mice and viral-mediated gene transfer. Given the essential role of SODs in cardiovascular disease, the concept of antioxidant therapies, that is, reinforcement of endogenous antioxidant defenses to more effectively protect against oxidative stress, is of substantial interest. However, the clinical evidence remains controversial. In this review, we will update the role of each SOD in vascular biologies, physiologies, and pathophysiologies such as atherosclerosis, hypertension, and angiogenesis. Because of the importance of metal cofactors in the activity of SODs, we will also discuss how each SOD obtains catalytic metal in the active sites. Finally, we will discuss the development of future SOD-dependent therapeutic strategies. Antioxid. Redox Signal. 15, 000–000.
Issue Date: 2011-04-07
Publisher: Mary Ann Liebert
Citation Info: Fukai, T. & Ushio-Fukai, M. 2011. Superoxide Dismutases: Role in Redox Signaling, Vascular Function and Diseases. Antioxidants and Redox Signaling. 15(6). DOI: 10.1089/ars.2011.3999.
Type: Article
Description: This is a copy of an article published in the Antioxidants and Redox Signaling © 2011 copyright Mary Ann Liebert, Inc.; Antioxidants and Redox Signaling is available online at: DOI: 10.1089/ars.2011.399
ISSN: 1523-0864
Sponsor: This research was supported by NIH R01 HL070187 (T.F.) and NIH R01 HL077524 (to M.U.-F.).
Date Available in INDIGO: 2012-03-21

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