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Review
. 2020 May:32:101508.
doi: 10.1016/j.redox.2020.101508. Epub 2020 Mar 19.

Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise

Zhen Yan  1 , Hannah R Spaulding  2
Affiliations
Review

Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise

Zhen Yan et al. Redox Biol. 2020 May.

Abstract

Extracellular superoxide dismutase (EcSOD) is the only extracellular scavenger of superoxide anion (O2.-) with unique binding capacity to cell surface and extracellular matrix through its heparin-binding domain. Enhanced EcSOD activity prevents oxidative stress and damage, which are fundamental in a variety of disease pathologies. In this review we will discuss the findings in humans and animal studies supporting the benefits of EcSOD induced by exercise training in reducing oxidative stress in various tissues. In particularly, we will highlight the importance of skeletal muscle EcSOD, which is induced by endurance exercise and redistributed through the circulation to the peripheral tissues, as a molecular transducer of exercise training to confer protection against oxidative stress and damage in various disease conditions.

Keywords: EcSOD; Endothelial cell activation; Endothelial dysfunction; Exercise; Oxidative stress.

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Conflict of interest statement

Declaration of competing interest The authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Enhanced skeletal muscle EcSOD expression by exercise promotes mitigation of oxidative stress and damage in a variety of peripheral tissues and disease conditions. Accumulating evidence supports that reduced EcSOD abundance and activities in tissues are associated with many disease conditions, and increased EcSOD activity is protective against oxidative stress and damage under these disease pathologies. Endurance exercise increases EcSOD abundance in skeletal tissue, which can be redistributed to peripheral tissues via the circulation to combat ROS and oxidative damage.
Fig. 2
Fig. 2
Elevated EcSOD abundance/activity prevents extracellular oxidative stress endothelial dysfunction and endothelial cell activation by scavenging superoxide anion. A) EcSOD originating from the skeletal muscle by exercise can be redistributed to nearby myofibers to the myocardium where it removes ROS and prevents myocyte impairment. B) Under normal conditions, NO generated in endothelial cells causes vasodilation in the adjacent smooth muscle cells in arteries. Increased superoxide reacts with nitric oxide (NO), produce peroxynitrite (OONO−), which inhibits vasodilation. Exercise-induced increase of EcSOD promotes removal of O2.- and preserved NO availability to effectively prevent endothelial dysfunction. C) O2.- stimulates pro-inflammatory cytokines and expression of cell surface adhesion molecules, such as VCAM-1, ICAM-1, and E-selectin. Cytokines recruits the leukocytes to interact with endothelial cells through the cell surface adhesion molecules, leading to a vicious cycle of endothelial cell activation as well as leukocyte transendothelial migration, causing tissue damage.
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