Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

Abstract

The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling. Antioxid. Redox Signal. 18, 1208–1246.

I. Introduction

II. General Adaptations to Exercise

III. Exercise, ROS, Antioxidant, and Housekeeping Systems

• A. ROS and antioxidants

• B. Thiols and redox signaling in exercise

• C. Oxidative damage and housekeeping

IV. ROS, Metabolism, and Exercise

• A. Sirtuins as redox-sensitive energy sensors of exercise

• B. Redox signaling and biogenesis of mitochondria

V. Exercise-Induced Inflammation and ROS

VI. The Crucial Role of Redox Regulation on New Cell Formation in Skeletal Muscle and Brain

VII. Exercise, ROS and Oxygen Sensing, HIF, and Vascular Endothelial Growth Factor

• A. Hypoxia in skeletal muscle

• B. HIF-1α-independent regulation of VEGF and angiogenesis

• C. p38γ MAPK/PGC-1α signaling regulation by physical exercise and its significance for mitochondrial biogenesis and angiogenesis in skeletal muscle

• D. Two-faced ROS in HIF activation

• E. Effect of exercise on HIF and VEGF signaling

VIII. Exercise, ROS, and Epigenetics

IX. Conclusion