Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation

Victor Galvan-Alvarez; Marcos Martin-Rincon; Angel Gallego-Selles; Miriam Martínez Canton; NaDer HamedChaman; Miriam Gelabert-Rebato; Mario Perez-Valera; Eduardo García-Gonzalez; Alfredo Santana; Hans-Christer Holmberg; Robert Boushel; Jostein Hallén; Jose A L Calbet

doi:10.1016/j.redox.2023.102859

Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation

Redox Biol. 2023 Oct:66:102859. doi: 10.1016/j.redox.2023.102859. Epub 2023 Aug 22.

Affiliations

¹ Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain.
² Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain; Department of Exercise Physiology, Faculty of Sports Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran.
³ Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain; Complejo Hospitalario Universitario Insular-Materno Infantil de Las Palmas de Gran Canaria, Clinical Genetics Unit, 35016, Las Palmas de Gran Canaria, Spain.
⁴ Department of Health Sciences, Luleå University of Technology, Sweden; School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada.
⁵ School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada.
⁶ Department of Physical Performance, The Norwegian School of Sport Sciences, Postboks, 4014 Ulleval Stadion, 0806, Oslo, Norway.
⁷ Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain; School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada; Department of Physical Performance, The Norwegian School of Sport Sciences, Postboks, 4014 Ulleval Stadion, 0806, Oslo, Norway. Electronic address: lopezcalbet@gmail.com.

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 pSer⁴⁰-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.

Keywords: Fatigue; Free radicals; High-intensity exercise; Ischaemia; Keap1; Nrf2; Performance; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antioxidants*
Calcium
Exercise* / physiology
Female
Humans
Kelch-Like ECH-Associated Protein 1* / physiology
Male
Muscle Proteins
Muscles* / physiology
NF-E2-Related Factor 2* / physiology

Substances

Antioxidants
Calcium
Kelch-Like ECH-Associated Protein 1
Muscle Proteins
NF-E2-Related Factor 2