Altering the redox state of skeletal muscle by glutathione depletion increases the exercise‐activation of PGC‐1α. Issue 12 (23rd December 2014)

• Record Type: Journal Article
• Authors: Strobel, Natalie A.; Matsumoto, Aya; Peake, Jonathan M.; Marsh, Susan A.; Peternelj, Tina‐Tinkara; Briskey, David; Fassett, Robert G.; Coombes, Jeff S.; Wadley, Glenn D.
• Is Part Of: Physiological reports. Volume 2:Issue 12(2014:Dec.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2014-12-23
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12224
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy212224-abs-0001"> <title>Abstract</title> <p>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 (<italic>P</italic> < 0.05). Within the control group, total glutathione was higher in the sedentary group compared to after exercise (<italic>P</italic> < 0.05). DEM treatment also significantly increased oxidative stress, as measured by increased plasma F<sub>2</sub>–isoprostanes (<italic>P</italic> < 0.05). Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor <italic>γ</italic> coactivator‐1<italic>α</italic> (PGC–1<italic>α</italic>) mRNA compared to the control animals that were exercised (<italic>P</italic> < 0.05). This study provides novel evidence that by lowering the endogenous antioxidant glutathione in skeletal muscle and inducing oxidative stress through exercise, PGC‐1<italic>α</italic> gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis.</p> </abstract>