52 research outputs found
The basic chemistry of exercise-induced DNA oxidation:oxidative damage, redox signalling and their interplay
Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signalling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (ĪOH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ĪOH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation
Influence of vitamin C and vitamin E on redox signalling:implications for exercise adaptations
The exogenous antioxidants vitamin C (ascorbate) and vitamin E (Ī±-tocopherol) often blunt favourable cell signalling responses to exercise, suggesting that redox signalling contributes to exercise adaptations. Current theories posit that this antioxidant paradigm interferes with redox signalling by attenuating exercise-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. The well-documented in vitro antioxidant actions of ascorbate and Ī±-tocopherol and characterisation of the type and source of the ROS/RNS produced during exercise theoretically enables identification of the redox-dependent mechanism responsible for the blunting of favourable cell signalling responses to exercise. This review aimed to apply this reasoning to determine how the aforementioned antioxidants might attenuate exercise-induced ROS/RNS production. The principal outcomes of this analysis are (1) neither antioxidant is likely to attenuate nitric oxide signalling either directly (reaction with nitric oxide) or indirectly (reaction with derivatives, e.g. peroxynitrite) (2) neither antioxidant reacts appreciably with hydrogen peroxide, a key effector of redox signalling (3) ascorbate but not Ī±-tocopherol has the capacity to attenuate exercise-induced superoxide generation and (4) alternate mechanisms, namely pro-oxidant side reactions and/or reduction of bioactive oxidised macromolecule adducts, are unlikely to interfere with exercise-induced redox signalling. Out of all the possibilities considered, ascorbate mediated suppression of superoxide generation with attendant implications for hydrogen peroxide signalling is arguably the most cogent explanation for blunting of favourable cell signalling responses to exercise. However, this mechanism is dependent on ascorbate accumulating at sites rich in NADPH oxidases, principal contributors to contraction mediated superoxide generation, and outcompeting nitric oxide and superoxide dismutase isoforms. The major conclusions of this review are: (1) direct evidence for interference of ascorbate and Ī±-tocopherol with exercise-induced ROS/RNS production is lacking (2) theoretical analysis reveals that both antioxidants are unlikely to have a major impact on exercise-induced redox signalling and (3) it is worth considering alternate redox-independent mechanisms
Ten āCheat Codesā for Measuring Oxidative Stress in Humans
Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive ācheat codesā for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated ādoā and ādonātā guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans
Ten āCheat Codesā for Measuring Oxidative Stress in Humans
Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive ācheat codesā for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated ādoā and ādonātā guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans
Editorial Redox Biology of Exercise
Redox biology is probably the most rapidly expanding field in biology. Indeed, the number of conferences, journals, and books devoted to redox biology is increasing and it is very often seen that major biology journals publish special issues on this area (e.g., Exercise is perhaps one of the most characteristic examples demonstrating that reactive species are not necessarily "harmful" entities, considering that the well-known benefits of regular exercise on muscle function and health are accompanied by repeated episodes of oxidative and nitrosative stress. In addition, an ongoing debate exists in the literature regarding the implications of antioxidant supplementation on physical performance and redox homeostasis. Considering that the redox biology of exercise is by nature multidisciplinary, this special issue is compiled of original and review articles combining chemical, analytical, biochemical, nutritional, physiological, and medical aspects relevant to reactive species biology. Reading through these papers the multiple facets of exercise redox biology are revealed. The review article by E. C. Gomes et al. presents the current state of knowledge on the redox biology of exercise. It provides a comprehensive perspective on the contribution of various intracellular and extracellular sources and the identity of oxidants produced by exercising animals and humans. It also focuses on the possible role of these exercise-induced oxidants in important training adaptations such as angiogenesis, mitochondria biogenesis, and muscle hypertrophy. This article lays the groundwork for the other articles of the special issue that address oxidant effects on exercise performance and redox homeostasis and diseases. Specifically, H. Pan et al. indicated that electrical stimulation of skeletal muscle cells increased the production of reactive species as well as the mRNA and protein levels of interleukin-6. The authors hypothesized that reactive species generation induced by skeletal muscle contraction may be one of the factors regulating musclederived interleukin-6 production and release. Using a more physiological relevant methodology, S. Mrakic-Sposta et al. employed an electron paramagnetic resonance technique for the rapid and noninvasive measurement of reactive species concentration directly in fresh human peripheral blood. Using this innovative approach, they reported that short-term high-intensity exercise increased reactive species production whereas the resting levels of reactive species decreased following supplementation with the antioxidant cofactor Ī±-lipoic acid
Principles for integrating reactive species into in vivo biological processes:examples from exercise physiology
The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question
The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses
Ī¤he aim of this study was to examine the effects of the consumption of foods of various glycemic index values on performance, Ī²-endorphin levels and substrate (fat and carbohydrate) utilization during prolonged exercise. Eight untrained healthy males underwent, in a randomized counterbalanced design, three experimental conditions under which they received carbohydrates (1.5 gr. kg-1 of body weight) of low glycemic index (LGI), high glycemic index (HGI) or placebo. Food was administered 30 min prior to exercise. Subjects cycled for 60 min at an intensity corresponding to 65% of VO2max, which was increased to 90% of VO2max, then they cycled until exhaustion and the time to exhaustion was recorded. Blood was collected prior to food consumption, 15 min prior to exercise, 0, 20, 40, and 60 min into exercise as well as at exhaustion. Blood was analyzed for Ī²-endorphin, glucose, insulin, and lactate. The mean time to exhaustion did not differ between the three conditions (LGI = 3.2 Ā± 0.9 min; HGI = 2.9 Ā± 0.9 min; placebo = 2.7 Ā± 0.7 min). There was a significant interaction in glucose and insulin response (P < 0.05) with HGI exhibiting higher values before exercise. Ī²-endorphin increased significantly (P < 0.05) at the end of exercise without, however, a significant interaction between the three conditions. Rate of perceived exertion, heart rate, ventilation, lactate, respiratory quotient and substrate oxidation rate did not differ between the three conditions. The present study indicates that ingestion of foods of different glycemic index 30 min prior to one hour cycling exercise does not result in significant changes in exercise performance, Ī²-endorphin levels as well as carbohydrate and fat oxidation during exercise
Quantitative Redox Biology of Exercise
Ā© Georg Thieme Verlag KG Stuttgart Ā· New York. Biology is rich in claims that reactive oxygen and nitrogen species are involved in every biological process and disease. However, many quantitative aspects of redox biology remain elusive. The important quantitative parameters you need to address the feasibility of redox reactions in vivo are: rate of formation and consumption of a reactive oxygen and nitrogen species, half-life, diffusibility and membrane permeability. In the first part, we explain the basic chemical kinetics concepts and algebraic equations required to perform "street fighting" quantitative analysis. In the second part, we provide key numbers to help thinking about sizes, concentrations, rates and other important quantities that describe the major oxidants (superoxide, hydrogen peroxide, nitric oxide) and antioxidants (vitamin C, vitamin E, glutathione). In the third part, we present the quantitative effect of exercise on superoxide, hydrogen peroxide and nitric oxide concentration in mitochondria and whole muscle and calculate how much hydrogen peroxide concentration needs to increase to transduce signalling. By taking into consideration the quantitative aspects of redox biology we can: i) refine the broad understanding of this research area, ii) design better future studies and facilitate comparisons among studies, and iii) define more efficiently the "borders" between cellular signaling and stress
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