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-c coactivator 1a (PGC-1a), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1a 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 proteinprotein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROSmediated activation of hypoxia-inducible factor 1a. 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, 1208Signal. 18, -1246

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress

“…According to microarray data, mdx muscle showed an upregulation in the response of a gene set related to glutathione metabolism possibly contributing to UPR and increased oxidized glutathione (GSSG) levels. The glutathione and thioredoxin superfamilies are the most abundant endogenous thiol antioxidants that maintain redox homeostasis and facilitate correct oxidative protein folding, which involve thiol-disulfide exchange reactions [4]. Several ER-resident glutathione and thioredoxin-dependent peroxidases, including peroxiredoxins and certain isoforms of GPX (i.e., GPX 7 and GPX8) play a critical role in oxidative protein folding [44].…”

“…Oxidative stress is a disruption of thiol redox circuits that results in impaired cell signaling and dysfunctional redox-control [4,5]. It is linked to several pathological processes including dysfunction of proteostasis and the accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER), resulting in ER stress [6].…”

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

“…EX is known to stimulate endothelial NOS activity and the expression of antioxidant enzymes [27,58]. Yet, EX is also known to transiently increase oxidative stress, and the beneficial adaptive changes can be prevented by a concomitant intake of antioxidants [29,63].…”

“…2l) and overall risk of CVD [39]. The lasting impact or memory of the biological molecular modeling induced by EX is, therefore, reflected by the overexpression of stress resistance pathways [40,[56][57][58] and might explain the better outcome in EX mice.…”

Glucose levels dictate cell fate following oxidative stress exposure by regulation of the sirtuin 3/p53 pathway

“…Oxidative damage is also a common feature of degenerative diseases (2) . Musculoskeletal tissues are regularly exposed to oxidative stress as a result of mechanical loading (3) . We hypothesized that high extracellular glucose levels would hinder the ability of cells to withstand oxidative stress leading to cell dysfunction and predisposing to tissue degeneration.…”