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

Strobel, Natalie, Matsumoto, Aya, Peake, Jonathan, Marsh, Susan, Peternelj, Tina, Briskey, David, Fassett, Robert, & Coombes, Jeff S. (2014) Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α. Physiological Reports, 2(12), e12224.

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We investigated the relationship between mitochondrial biogenesis, cell signalling 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 treated with 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 reducing 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.

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ID Code: 79500
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website
Additional URLs:
Keywords: reactive oxygen species; diethy l maleate; exercise; PGC-1 α
DOI: 10.14814/phy2.12224
ISSN: 2051-817X
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > HUMAN MOVEMENT AND SPORTS SCIENCE (110600) > Exercise Physiology (110602)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 [The Authors]
Copyright Statement: All articles accepted from 14 August 2012 are published under the terms of the Creative Commons Attribution License. All articles accepted before this date, were published under a Creative Commons Attribution Non-Commercial License.
Deposited On: 16 Dec 2014 00:22
Last Modified: 29 Jan 2015 03:56

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