title: Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle.
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.
authors.affiliation: Antioxidant Research Group, School of Human Movement Studies, The University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia, tina.peternelj@uqconnect.edu.au.
authors.forename: Tina Tinkara
authors.initials: TT
authors.lastname: Peternelj
authors.forename: Susan A
authors.initials: SA
authors.lastname: Marsh
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Strobel
authors.forename: Aya
authors.initials: A
authors.lastname: Matsumoto
authors.forename: David
authors.initials: D
authors.lastname: Briskey
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Dalbo
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tucker
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D008298:Maleates / Q000008:administration & dosage; D018482:Muscle, Skeletal / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis*; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D011499:Protein Processing, Post-Translational; D051381:Rats
chemical_list: D008298:Maleates; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C014476:diethyl maleate; D005978:Glutathione