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Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle

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Abstract

Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. DEM and exercise both reduced intracellular glutathione and increased O-GlcNAc. DEM upregulated OGT protein expression. The effects of the interventions were significant 4 h after exercise (P < 0.05). The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise.

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Acknowledgments

We thank Gary Wilson for his technical assistance. This work was supported by the School of Human Movement Studies, The University of Queensland (Tina-Tinkara Peternelj, Natalie Strobel, Aya Matsumoto, David Briskey and Jeff Coombes), Institute for Health and Social Science Research, Central Queensland University (Vincent Dalbo and Patrick Tucker), and the College of Pharmacy, Washington State University (Susan Marsh).

Conflict of Interest

There have been no conflicts of interest and sources of funding for all authors involved in the preparation of this manuscript.

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Authors and Affiliations

  1. Antioxidant Research Group, School of Human Movement Studies, The University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia

    Tina Tinkara Peternelj, Natalie A. Strobel, David Briskey & Jeff S. Coombes

  2. Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, WA, USA

    Susan A. Marsh

  3. School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia

    Natalie A. Strobel

  4. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

    Aya Matsumoto

  5. School of Medicine, The University of Queensland, Brisbane, QLD, Australia

    David Briskey

  6. Clinical Biochemistry Laboratory, Central Queensland University, Rockhampton, QLD , Australia

    Vincent J. Dalbo & Patrick S. Tucker

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  1. Tina Tinkara Peternelj
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Peternelj, T.T., Marsh, S.A., Strobel, N.A. et al. Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle. Mol Cell Biochem 400, 265–275 (2015). https://doi.org/10.1007/s11010-014-2283-0

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