Superoxide dismutases

Role in redox signaling, vascular function, and diseases

Research output: Contribution to journalReview article

595 Citations (Scopus)

Abstract

Excessive reactive oxygen species Revised abstract, especially superoxide anion (O 2 •-), play important roles in the pathogenesis of many cardiovascular diseases, including hypertension and atherosclerosis. Superoxide dismutases (SODs) are the major antioxidant defense systems against O 2 •-, 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 O 2 •- H 2O 2, 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.

Original languageEnglish (US)
Pages (from-to)1583-1606
Number of pages24
JournalAntioxidants and Redox Signaling
Volume15
Issue number6
DOIs
StatePublished - Sep 15 2011
Externally publishedYes

Fingerprint

Vascular Diseases
Superoxide Dismutase
Oxidation-Reduction
Antioxidants
Metals
Atherosclerosis
Protein Isoforms
Cardiovascular Diseases
Cell signaling
Hypertension
Gene transfer
Peroxynitrous Acid
Mammals
Oxidative stress
Viral Genes
Physiology
Superoxides
Blood Vessels
Reactive Oxygen Species
Catalytic Domain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Superoxide dismutases : Role in redox signaling, vascular function, and diseases. / Fukai, Tohru; Fukai, Masuko.

In: Antioxidants and Redox Signaling, Vol. 15, No. 6, 15.09.2011, p. 1583-1606.

Research output: Contribution to journalReview article

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