Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness

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  • Victor Galvan-Alvarez
  • Angel Gallego-Selles
  • Miriam Martinez-Canton
  • Eduardo García-Gonzalez
  • Miriam Gelabert-Rebato
  • Jesus Gustavo Ponce-Gonzalez
  • Larsen, Steen
  • David Morales-Alamo
  • Jose Losa-Reyna
  • Ismael Perez-Suarez
  • Cecilia Dorado
  • Mario Perez-Valera
  • Hans Christer Holmberg
  • Robert Boushel
  • Pedro de Pablos Velasco
  • Helge, Jørn Wulff
  • Marcos Martin-Rincon
  • Jose A.L. Calbet

Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.

TidsskriftFree Radical Biology and Medicine
Sider (fra-til)282-291
Antal sider10
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was financed by grants from the Ministerio de Economía y Competitividad ( DEP2015-71171-R ; DEP2017-86409-C2-1-P ; PID2021-125354OB-C21 ; PI14/01509 ), University of Las Palmas de Gran Canaria ( ULPAPD-08/01–4 ), Agencia Canaria de Investigación, Innovación y Sociedad de la Infomación ( ProID2017010106 ), FEDER , Swedish Olympic Committee (Ref: 070–4058960), Consejo Superior de Deportes ( EXP_75097 ), European Union NextGenerationEU , Gobierno de España , Ministerio de Cultura y Deporte, Plan de Recuperación , Transformación y Resilencia . Authors would like to acknowledge Cabildo de Gran Canaria (grant 12/22 ) and FDCAN (Fondo de Desarrollo de Canarias) for the economic support to this research work. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The technical assistance by Jose Navarro de Tuero is greatly appreciated.

Publisher Copyright:
© 2023 The Authors

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