title: Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α.
abstract: We investigated the relationship between markers of mitochondrial biogenesis, cell signaling, and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats + DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h after exercise; and (6) exercise rats + DEM euthanized 4 h after exercise. Exercising animals ran on the treadmill at a 10% gradient at 20 m/min for the first 30 min. The speed was then increased every 10 min by 1.6 m/min until exhaustion. There was a reduction in total glutathione in the skeletal muscle of DEM treated animals compared to the control animals (P < 0.05). Within the control group, total glutathione was higher in the sedentary group compared to after exercise (P < 0.05). DEM treatment also significantly increased oxidative stress, as measured by increased plasma F2-isoprostanes (P < 0.05). Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) mRNA compared to the control animals that were exercised (P < 0.05). This study provides novel evidence that by lowering the endogenous antioxidant glutathione in skeletal muscle and inducing oxidative stress through exercise, PGC-1α gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis.
authors.affiliation: Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Strobel
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Aya
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Peake
authors.affiliation: College of Pharmacy, Washington State University, Spokane, Washington, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Marsh
authors.affiliation: Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Tina-Tinkara
authors.initials: TT
authors.lastname: Peternelj
authors.affiliation: Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Briskey
authors.affiliation: Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fassett
authors.affiliation: Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
authors.affiliation: Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Wadley
keywords: Diethyl maleate; PGC‐1α; exercise; reactive oxygen species