Terminal differentiation program of skeletal myogenesis is negatively regulated by O-GlcNAc glycosylation

Ogawa, Masamichi; Mizofuchi, Hidenori; Kobayashi, Yuki; Tsuzuki, Genta; Yamamoto, Mayumi; Wada, Shinpei; Kamemura, Kazuo

doi:10.1016/j.bbagen.2011.10.011

Cited by 39 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OGA significantly decreased in diabetic muscle; therefore, we focused on OGA in in vitro studies. By use of C2C12 myoblasts as a myogenesis model, we showed that OGA levels increased with decreased cellular O-GlcNAcylation during myogenesis, which was consistent with a previous finding [42]. In our study, mitochondrial biogenesis was possibly induced in response to the higher energy demand required for myogenesis, whereas were transfected with pcDNA3.1-Oga for 72 h with or without insulin challenge for another 10 min, followed by detection of p-Akt/Akt and p-GSK-3α/β/GSK-3α/β.…”

Section: Discussionsupporting

confidence: 80%

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

et al. 2016

View full text Add to dashboard Cite

Aims/hypothesis O-GlcNAcylation is implicated in modulating mitochondrial function, which is closely involved in regulating muscle metabolism. The presence of O-GlcNAcase (OGA), the enzyme involved in the removal of O-GlcNAc, in mitochondria was recently confirmed in rats. In the present study, we investigated the regulation of myogenesis and muscle insulin sensitivity to OGA in mice, with a focus on mitochondria. Methods C57BL/6J mice fed a high-fat diet for 4 months were used to observe mitochondrial density, activity and O-GlcNAcylation in muscle. Small interfering RNA and overexpression vectors were used to modulate protein content in vitro. Results High-fat feeding decreased the OGA level and largely increased mitochondrial O-GlcNAcylation in mouse skeletal muscle that was accompanied by decreased levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), decreased mitochondrial density and disrupted mitochondrial complex activities. Knockdown of OGA in C2C12 myoblasts promoted PGC-1α degradation, resulting in the suppression of mitochondrial biogenesis and myogenesis, whereas neither knockdown of O-GlcNAc transferase nor overexpression of OGA had significant effects on myogenesis. Mitochondrial dysfunction as evidenced by decreased ATP content and increased reactive oxygen species production, and increased lipid and protein oxidation was observed in both myoblasts and myotubes after OGA knockdown. Meanwhile, elevated O-GlcNAcylation through either OGA knockdown or treatment with the OGA inhibitor PUGNAc and the O-GlcNAc transferase substrate D-GlcNAc suppressed myotube insulin signalling transduction and glucose uptake. OGA overexpression had no significant effect on insulin sensitivity but sufficiently improved the insulin resistance induced by D-GlcNAc treatment. Conclusions/interpretation These data suggest that OGA can modulate mitochondrial density via PGC-1α and mitochondrial function via protein O-GlcNAcylation. In this manner, OGA appears to play a key role in myogenesis and the development of muscle insulin resistance.

show abstract

Section: Discussionsupporting

confidence: 80%

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…1). Changes in the extent of protein O-GlcNAc modification occurring concomitantly with increased expression OGT and OGA have been observed during the differentiation of mesenchymal stem cells toward myoblasts or chondrocytes (26,27). During the time course of differentiation in MC3T3E1 cells the expression of OGT and OGA did not change (Fig.…”

Section: Resultsmentioning

confidence: 83%

“…In adipocytes, elevated O-GlcNAcylation of adipogenic CCAAT/enhancer-binding protein ␤ and peroxisome proliferator-activated receptor ␥ decreased the DNA binding and transcriptional activity, respectively, and hindered terminal adipocyte differentiation (24,25). In C2C12 myoblasts, chronic inhibition of OGA selectively reduced expression of myogenic markers myogenin and MRF4 and blocked myotube formation (26). In ATDC5 chondrocytes, pharmacological inhibition of OGA increased the progression of chondrogenesis (59) and enhanced the expression and activity of matrix metalloprotease (MMP) 2 and 9 (27).…”

Section: Discussionmentioning

confidence: 99%

Identification of O-Linked N-Acetylglucosamine (O-GlcNAc)-modified Osteoblast Proteins by Electron Transfer Dissociation Tandem Mass Spectrometry Reveals Proteins Critical for Bone Formation

Nagel

Schilling²,

Comte‐Walters

et al. 2013

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

(3), O-GlcNAc modification is now appreciated as a nutrient-responsive mechanism for modulating signal transduction (4, 5) and transcriptional regulation (6, 7). In contrast to N-and O-linked glycosylation taking place in the endoplasmic reticulum and Golgi apparatus, reversible O-GlcNAcylation occurs in the cytoplasm and nucleus and is catalyzed by O-GlcNAc transferase (OGT), which transfers GlcNAc from UDP-GlcNAc to Ser/Thr residues, and O-GlcNAcase (OGA), which removes it. These highly conserved enzymes are expressed in all mammalian tissues (8 -11).The OGT gene encodes three splice variants differing in the number of N-terminal tetratricopeptide repeats that mediate protein-protein interactions and subcellular localization (8,12). The full-length nucleocytoplasmic form of OGT is OGlcNAc-modified, tyrosine-phosphorylated, and dynamically redistributed within the cell upon insulin stimulation (2,(13)(14)(15). Ablation of OGT is embryonically lethal or developmentally limiting in animal models (10,16,17) with the noted exception of Caenorhabditis elegans. In C. elegans, the phenotypes of oga-1 and ogt-1 null mutants suggest the enzymes are involved in macronutrient storage and life span (18 -20), and subsequent studies revealed the presence of O-GlcNAc modFrom the

show abstract

“…In addition, O-GlcNAc modification of C/EBPβ, a key transcription factor of adipogenesis at the earlier stage, negatively regulates DNA binding activity of C/EBPβ (Li et al, 2009). In contrast to osteogenesis and adipogenesis, mouse C2C12 myoblasts show a drastic decrease in the level of OGlcNAc modification during skeletal myogenesis (Ogawa et al, 2012). Pharmacological (Yanagisawa and Yu, 2009).…”

Section: O-glcnacylation Enzymes In the Nucleus Cytosol And Mitochomentioning

confidence: 94%

Intracellular and extracellular O-linked N-acetylglucosamine in the nervous system

Ogawa

Sawaguchi

Kamemura

et al. 2015

Experimental Neurology

Self Cite

View full text Add to dashboard Cite

Terminal differentiation program of skeletal myogenesis is negatively regulated by O-GlcNAc glycosylation

Cited by 39 publications

References 35 publications

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

Identification of O-Linked N-Acetylglucosamine (O-GlcNAc)-modified Osteoblast Proteins by Electron Transfer Dissociation Tandem Mass Spectrometry Reveals Proteins Critical for Bone Formation

Intracellular and extracellular O-linked N-acetylglucosamine in the nervous system

Contact Info

Product

Resources

About