Exercise training increases protein O-GlcNAcylation in rat skeletal muscle.
Protein O-GlcNAcylation has emerged as an important intracellular signaling system with both physiological and pathophysiological functions, but the role of protein O-GlcNAcylation in skeletal muscle remains elusive. In this study, we tested the hypothesis that protein O-GlcNAcylation is a dynamic signaling system in skeletal muscle in exercise and disease. Immunoblotting showed different protein O-GlcNAcylation pattern in the prototypical slow twitch soleus muscle compared to fast twitch EDL from rats, with greater O-GlcNAcylation level in soleus associated with higher expression of the modulating enzymes O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and glutamine fructose-6-phosphate amidotransferase isoforms 1 and 2 (GFAT1, GFAT2). Six weeks of exercise training by treadmill running, but not an acute exercise bout, increased protein O-GlcNAcylation in rat soleus and EDL There was a striking increase in O-GlcNAcylation of cytoplasmic proteins ~50 kDa in size that judged from mass spectrometry analysis could represent O-GlcNAcylation of one or more key metabolic enzymes. This suggests that cytoplasmic O-GlcNAc signaling is part of the training response. In contrast to exercise training, postinfarction heart failure (HF) in rats and humans did not affect skeletal muscle O-GlcNAcylation level, indicating that aberrant O-GlcNAcylation cannot explain the skeletal muscle dysfunction in HF Human skeletal muscle displayed extensive protein O-GlcNAcylation that by large mirrored the fiber-type-related O-GlcNAcylation pattern in rats, suggesting O-GlcNAcylation as an important signaling system also in human skeletal muscle.
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway k.h.hortemo@medisin.uio.no.
Kristin Halvorsen
KH
Hortemo
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Per Kristian
PK
Lunde
Department of Biosciences, University of Oslo, Oslo, Norway.
Jan Haug
JH
Anonsen
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Heidi
H
Kvaløy
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
Morten
M
Munkvik
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
Tommy Aune
TA
Rehn
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Ivar
I
Sjaastad
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Ida Gjervold
IG
Lunde
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Bjørknes College, Oslo, Norway.
Jan Magnus
JM
Aronsen
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Ole M
OM
Sejersted
Exercise; O‐GlcNAcylation; fatigue; heart failure; skeletal muscle
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