Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α

Natalie A Strobel; Aya Matsumoto; Jonathan M Peake; Susan A Marsh; Tina-Tinkara Peternelj; David Briskey; Robert G Fassett; Jeff S Coombes; Glenn D Wadley

doi:10.14814/phy2.12224

Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α

Physiol Rep. 2014 Dec 23;2(12):e12224. doi: 10.14814/phy2.12224. Print 2014 Dec 1.

Authors

Natalie A Strobel¹, Aya Matsumoto², Jonathan M Peake³, Susan A Marsh⁴, Tina-Tinkara Peternelj¹, David Briskey⁵, Robert G Fassett¹, Jeff S Coombes¹, Glenn D Wadley⁶

Affiliations

¹ Exercise and Oxidative Stress Research Group, School of Human Movement Studies, The University of Queensland, St. Lucia, Queensland, Australia.
² Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
³ School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
⁴ College of Pharmacy, Washington State University, Spokane, Washington, USA.
⁵ 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.
⁶ 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.

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.

Keywords: Diethyl maleate; PGC‐1α; exercise; reactive oxygen species.