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Title: Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation
Authors: Galván Álvarez, Víctor 
Martín Rincón, Marcos 
Gallego Selles, Ángel 
Martínez Canton, Miriam
HamedChaman, NaDer
Gelaber Rebato,Miriam 
Pérez Valera, Mario 
García González, Eduardo 
Santana Rodríguez, Alfredo 
Holmberg ,Hans-Christer 
Boushel ,Robert 
López Calbet, José Antonio 
UNESCO Clasification: 241106 Fisiología del ejercicio
Keywords: Fatigue
Free Radicals
High-Intensity Exercise
Keap1, et al
Issue Date: 2023
Journal: Redox Biology
Abstract: When high-intensity exercise is performed until exhaustion a “functional reserve” (FR) or capacity to produce power at the same level or higher than reached at exhaustion exists at task failure, which could be related to reactive oxygen and nitrogen species (RONS)-sensing and counteracting mechanisms. Nonetheless, the magnitude of this FR remains unknown. Repeated bouts of supramaximal exercise at 120% of VO2max interspaced with 20s recovery periods with full ischaemia were used to determine the maximal FR. Then, we determined which muscle phenotypic features could account for the variability in functional reserve in humans. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation (near-infrared spectroscopy) were measured, and resting muscle biopsies were obtained from 43 young healthy adults (30 males). Males and females had similar aerobic (VO2max per kg of lower extremities lean mass (LLM): 166.7 ± 17.1 and 166.1 ± 15.6 ml kg LLM−1.min−1, P = 0.84) and anaerobic fitness (similar performance in the Wingate test and maximal accumulated oxygen deficit when normalized to LLM). The maximal FR was similar in males and females when normalized to LLM (1.84 ± 0.50 and 2.05 ± 0.59 kJ kg LLM−1, in males and females, respectively, P = 0.218). This FR depends on an obligatory component relying on a reserve in glycolytic capacity and a putative component generated by oxidative phosphorylation. The aerobic component depends on brain oxygenation and phenotypic features of the skeletal muscles implicated in calcium handling (SERCA1 and 2 protein expression), oxygen transport and diffusion (myoglobin) and redox regulation (Keap1). The glycolytic component can be predicted by the protein expression levels of pSer [40]-Nrf2, the maximal accumulated oxygen deficit and the protein expression levels of SOD1. Thus, an increased capacity to modulate the expression of antioxidant proteins involved in RONS handling and calcium homeostasis may be critical for performance during high-intensity exercise in humans.
ISSN: 2213-2317
DOI: 10.1016/j.redox.2023.102859
Source: Redox Biology[ISSN 2213-2317],v. 66, (Octubre 2023)
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