Redox basis of exercise physiology.
Ontology highlight
ABSTRACT:
SUBMITTER: Margaritelis NV
PROVIDER: S-EPMC7284946 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Significance: This review considers how some systems controlling pulmonary vascular function are potentially regulated by redox processes to examine how and why conditions such as prolonged hypoxia, pathological mediators, and other factors promoting vascular remodeling contribute to the development of pulmonary hypertension (PH). Recent Advances and Critical Issues: Aspects of vascular remodeling induction mechanisms described are associated with shifts in glucose metabolism through the pentose phosphate pathway and increased cytosolic NADPH generation by glucose-6-phosphate dehydrogenase, increased glycolysis generation of cytosolic NADH and lactate, mitochondrial dysfunction associated with superoxide dismutase-2 depletion, changes in reactive oxygen species and iron metabolism, and redox signaling. Future Directions: The regulation and impact of hypoxia-inducible factor and the function of cGMP-dependent and redox regulation of protein kinase G are considered for their potential roles as key sensors and coordinators of redox and metabolic processes controlling the progression of vascular pathophysiology in PH, and how modulating aspects of metabolic and redox regulatory systems potentially function in beneficial therapeutic approaches.
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Project description:PurposeThis review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema.MethodData from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by "safety factors" in physiological conditions, (2) consider how waning of "safety factors" inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans.ResultsExercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema.ConclusionData from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air-blood barrier.
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Project description:Physical exercise represents one of the strongest physiological stimuli capable to induce functional and structural modifications in all biological systems. Indeed, beside the traditional genetic mechanisms, physical exercise can modulate gene expression through epigenetic modifications, namely DNA methylation, post-translational histone modification and non-coding RNA transcripts. Initially considered as merely damaging molecules, it is now well recognized that both reactive oxygen (ROS) and nitrogen species (RNS) produced under voluntary exercise play an important role as regulatory mediators in signaling processes. While robust scientific evidences highlight the role of exercise-associated redox modifications in modulating gene expression through the genetic machinery, the understanding of their specific impact on epigenomic profile is still at an early stage. This review will provide an overview of the role of ROS and RNS in modulating the epigenetic landscape in the context of exercise-related adaptations.
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Project description:RationaleExercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition.ObjectivesOur goals were to establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during EIB and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during EIB.MethodsInduced sputum was used to measure mast cell mediators and eicosanoids at baseline and 30 minutes after exercise challenge in 25 individuals with asthma with EIB. In a randomized, double-blind crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine or two matched placebos were administered for two doses before exercise challenge.Main resultsThe percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of EIB. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin E(2) and thromboxane B(2) significantly decreased in the airways, and there was an increase in columnar epithelial cells in the airways. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways.ConclusionsThese data indicate that epithelial cells, mast cell mediators, and eicosanoids are released into the airways during EIB, supporting an inflammatory basis for EIB.
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Project description:Ischemic heart disease and stroke are the number 1 and number 2 causes of death worldwide, respectively. A lifelong commitment to exercise reduces the risk of these adverse events and is also associated with several cardiometabolic improvements, including reductions in blood pressure, cholesterol, and inflammatory markers, as well as improved glucose control. Routine exercise also reduces the risk of developing comorbidities that increase the risk of cardiovascular or cerebrovascular disease. While the benefits of a lifelong commitment to exercise are well documented, there is a complex interaction between exercise and stroke risk, such that the risk of ischemic or hemorrhagic stroke may increase acutely during or immediately following exercise. In this article, we discuss the physiological responses to different types of exercise, as well as the determinants of resting and exertional cerebrovascular perfusion, and explore the complex interaction between atrial fibrillation, exercise, and stroke risk. Finally, we highlight the increased risk of stroke during different types of exercise, as well as factors that may alleviate this risk.
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Project description:Data Access Committee EGAC00001002606
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Project description:Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.
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Project description:Background:The aim of this study was to evaluate exercise physiology students' perceptions of two simulation-based learning modules focused on communication and interpersonal skills during history taking. Methods:A prospective, repeated-measures cohort study was conducted with 15 participants. The study evaluated two simulation-based learning modules in a 1-year Graduate Diploma of Exercise Science program. Surveys were administered at four time points: prior to each module and following each module. Students rated their confidence in communication and history taking, and perception of preparedness for practice, motivation for learning, and benefits of undertaking simulation-based learning. Quantitative data were analyzed descriptively and by using repeated measures tests. Qualitative data underwent thematic analyses. Results:Students reported a significant improvement in their confidence in communication (P?=?0.043) and in two parameters related to history taking (P?=?0.034 and 0.035) following the completion of the two modules. There was 96% agreement that the simulation-based learning better prepared students for practice as an exercise physiologist. Significant changes occurred in all aspects of motivation for learning (P ranging from <?0.001 to 0.036) except for usefulness, where there was a ceiling effect (medians of 7 on a 7-point scale). Qualitative analysis demonstrated benefit to participants around themes of experiential learning, realism, opportunity to develop clinical skills, and debriefing. Students also made suggestions with respect to the activity structure of the simulation-based learning modules. Conclusions:The results of this study indicated that simulation-based learning employing SPs increased the confidence and preparedness of exercise physiology students for conducting history taking, a requisite exercise physiology skill. Future studies should include behavioral measures of skill attainment and include follow-up evaluation to appraise the application of these skills into clinical practice.
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