Quantitative Redox Biology of Exercise

Abstract

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.

Sustaining efficient immune functions with regular physical exercise in the COVID‐19 era and beyond

“…However, we cannot exclude the key role of the redox signals hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO) in adjusting the extension of oxidative stress and the inflammation processes following any type of exercise 36 . Both H 2 O 2 and NO are reactive oxygen and nitrogen species (ROS/RNS) extensively produced in contractile muscles, vascular endothelium, cardiomyocytes (heart), lungs, plasma, etc during exercise, that, due to their low reactivity and high diffusibility in aqueous systems, could exert long‐range redox signalling effects in order to provide a proper and overall antioxidant, inflammatory and cytoprotective responses against potentially harmful oxidative stress 37 . Interestingly, the in situ antioxidant capacity of all those aforementioned sites of ROS/RNS production will exactly determine the intensity of the integrated redox signal—here, understand, the effective concentration of H 2 O 2 and NO produced—that will emanate from the active cells and tissues during exercise.…”

The redox signal: A physiological perspective

“…oxidized state due to production of reactive species even at rest or is it a fluctuation within the safe, non‐damaging limits of oxidative and reductive eustress? Since such quantitative information is absent, the conceptual frameworks used commonly to describe oxidative stress (e.g., the “oxidants/antioxidants seesaw” model and the “RONS triangle” model) are also of limited translational potential 20,21 …”

“…Since such quantitative information is absent, the conceptual frameworks used commonly to describe oxidative stress (e.g., the "oxidants/ antioxidants seesaw" model and the "RONS triangle" model) are also of limited translational potential. 20,21 It becomes clear that specificity is lacking as regards to oxidative stress. So, where does oxidative stress stand during this more accurate turning point of the redox biology research?…”

High intensity muscle stimulation activates a systemic Nrf2-mediated redox stress response

“…Exercise induces beneficial adaptations through redox signaling cascades that are mediated by the redox stress response transcription factor nuclear erythroid related factor 2 (Nrf2) [1][2][3]. The redox stress response system is a critical cytoprotective mechanism that protects both the cell from endogenous and environmental redox stressors and contributes to adaptive processes to exercise [4,5]. The redox signal transduction cascade is a highly complex and coordinated system involving the generation of reactive oxygen species, the oxidation of redox-relay molecules or direct oxidation of sensor molecules with thiol switches like Kelch-like ECHassociated protein 1 (Keap1), and effector molecules that change activity, localization, proteinprotein interactions, or protein turnover in response to the redox signaling cascade [6,7].…”

“…The redox signal transduction cascade is a highly complex and coordinated system involving the generation of reactive oxygen species, the oxidation of redox-relay molecules or direct oxidation of sensor molecules with thiol switches like Kelch-like ECHassociated protein 1 (Keap1), and effector molecules that change activity, localization, proteinprotein interactions, or protein turnover in response to the redox signaling cascade [6,7]. The overall physiological adaptation resulting from redox signaling cascades depends on the rate of accumulation of these reactive species, and the steady-state levels of enzymatic and nonenzymatic antioxidants [4], as well as the basal oxidation state of proteins with thiol-based redox switches [7][8][9].…”