title: OGT and OGA expression in postmenopausal skeletal muscle associates with hormone replacement therapy and muscle cross-sectional area.
abstract: Protein glycosylation via O-linked N-acetylglucosaminylation (O-GlcNAcylation) is an important post-translational regulatory mechanism mediated by O-GlcNAc transferase (OGT) and responsive to nutrients and stress. OGT attaches an O-GlcNAc moiety to proteins, while O-GlcNAcase (OGA) catalyzes O-GlcNAc removal. In skeletal muscle of experimental animals, prolonged increase in O-GlcNAcylation associates with age and muscle atrophy. Here we examined the effects of hormone replacement therapy (HRT) and power training (PT) on muscle OGT and OGA gene expression in postmenopausal women generally prone to age-related muscle weakness. In addition, the associations of OGT and OGA gene expressions with muscle phenotype were analyzed. Twenty-seven 50-57-year-old women participated in a yearlong randomized placebo-controlled trial: HRT (n=10), PT (n=8) and control (n=9). OGT and OGA mRNA levels were measured from muscle samples obtained at baseline and after one year. Knee extensor muscle cross-sectional area (CSA), knee extension force, running speed and vertical jumping height were measured. During the yearlong intervention, HRT suppressed the aging-associated upregulation of OGT mRNA that occurred in the controls. The effects of PT were similar but weaker. HRT also tended to increase the OGA mRNA level compared to the controls. The change in the ratio of OGT to OGA gene expressions correlated negatively with the change in muscle CSA. Our results suggest that OGT and OGA gene expressions are associated with muscle size during the critical postmenopausal period. HRT and PT influence muscle OGT and OGA gene expression, which may be one of the mechanisms by which HRT and PT prevent aging-related loss of muscle mass.
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland. Electronic address: minna.h.m.toivonen@gmail.com.
authors.forename: Minna H M
authors.initials: MH
authors.lastname: Toivonen
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Pöllänen
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Ahtiainen
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Suominen
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, 10 Chittaway Road, Ourimbah NSW 2258, Australia.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Taaffe
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Sulin
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Sports and Exercise Medicine, Oulu Deaconess Institute, Uusikatu 46, P. O. Box 365, 90101 Oulu, Finland; Department of Health Sciences, University of Oulu, Aapistie 5 A, P. O. Box 5000, 90014, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Takala
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Urho M
authors.initials: UM
authors.lastname: Kujala
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Yliopistonranta 1, P. O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Markku I
authors.initials: MI
authors.lastname: Tammi
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Sarianna
authors.initials: S
authors.lastname: Sipilä
authors.affiliation: Department of Health Sciences and Gerontology Research Centre, University of Jyväskylä, P. O. Box 35, 40014, Finland.
authors.forename: Vuokko
authors.initials: V
authors.lastname: Kovanen
mesh_terms: D000367:Age Factors; D015914:Estrogen Replacement Therapy; D005260:Female; D005387:Finland; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D008875:Middle Aged; D009119:Muscle Contraction; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D059385:Plyometric Exercise; D017698:Postmenopause / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases
keywords: Aging; CO; CSA; Estrogen; GAPDH; HRT; Muscle atrophy; Muscle cross-sectional area; O-GlcNAc; O-GlcNAc transferase; O-GlcNAcase; O-linked N-acetylglucosamine; OGA; OGT; PI3K; PT; Plyometric power training; Postmenopausal hormone replacement therapy; control; cross-sectional area; glyceraldehyde 3-phosphate dehydrogenase; hormone replacement therapy; phosphatidylinositol-3-kinase; power training