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

By T. Fukai, M. Ushio-Fukai. Antioxidants and Redox Signaling, 2011

1,887 citations recorded by the source corpus.

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, 1583–1606.

Subfields: Molecular Biology, Nutrition and Dietetics, Physiology

View Paper: https://www.semanticscholar.org/paper/5416fbde1172d4f9a4107ea356beee558edde41b

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Citations in the corpus

Vascular oxidative stress, nitric oxide and atherosclerosis. (2014, background): “SOD2 (Mn-SOD) is expressed in the mitochondrial matrix, whereas SOD3 (EC-SOD) is found in extracellular matrix, on cell surface and in extracellular fluids [74].”
Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. (2018, background): “SOD3 is the major SOD in the vascular extracellular space [95].”
Oxidative stress in angiogenesis and vascular disease. (2014, background): “Usually, superoxide anion is rapidly removed through dismutation to hydrogen peroxide, either spontaneously or by superoxide dismutases (SOD).(8,9) Neutrophil-secreted myeloperoxidase further converts hydrogen peroxide and chloride into highly reactive hypochlorite.”
Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling (2018, neutral): “In patients with coronary artery disease, the activity of SOD3 was also found to be reduced, whereas SOD1 and SOD2 remain unaffected (Fukai and Ushio-Fukai, 2011).”
Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. (2014, background): “H2O2 is generated through spontaneous or superoxide dismutase (SOD)catalyzed dismutation of O2 · (143).”
Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction (2015, background): “However, extracellular SOD, which mainly occurs in tissue ([36,37]; reviewed in [38,39]), can also be found in plasma under specific pathological conditions [40] and contribute to the elimination of O2• .”