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- Title
O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense.
- Authors
Peternelj, Tina Tinkara; Marsh, Susan A.; Morais, Christudas; Small, David M.; Dalbo, Vincent J.; Tucker, Patrick S.; Coombes, Jeff S.
- Abstract
A growing body of evidence demonstrates the involvement of protein modification with O-linked β- N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. Surprisingly, O-GlcNAc levels were significantly increased only with glucosamine, whilst other treatments showed no effect. Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. This could represent an important homeostatic regulation of the cellular defense system.
- Subjects
MYOBLASTS; OXIDATIVE stress; PHYSIOLOGICAL effects of antioxidants; PROTEIN analysis; MUSCLE cells
- Publication
Biochemistry & Cell Biology, 2015, Vol 93, Issue 1, p63
- ISSN
0829-8211
- Publication type
Article
- DOI
10.1139/bcb-2014-0106