title: Influence of corticosteroids on myonuclear domain size in the rat diaphragm muscle.
abstract: Skeletal muscle fibers are multinucleated. Each myonucleus regulates gene products and protein expression in only a restricted portion of the muscle fiber, the myonuclear domain (MND). In the rat diaphragm muscle (DIAm), corticosteroid (CoS) treatment causes atrophy of fibers containing myosin heavy chain (MHC): MHC2X and/or MHC2B. We hypothesized that DIAm fiber MND size is maintained during CoS-induced atrophy. Adult male rats received methylprednisolone for 11 days at 1 (CoS-Low, n = 8) or 8 mg x kg(-1) x day(-1) (CoS-High, n = 8). Age-matched (CTL-AgeM, n = 8), sham-operated (SHAM-AgeM, n = 8), and weight-matched (CTL-WtM, n = 8) animals served as controls. In single DIAm fibers, cross-sectional area (CSA), MND size, and MHC expression were determined. Fiber CSA and MND size were similar in CTL-AgeM and SHAM-AgeM groups. Only fibers containing MHCslow or MHC2A displayed smaller CSA in CTL-WtM than in CTL-AgeM and SHAM-AgeM groups, and MND size was reduced in all fibers. Thus fibers containing MHCslow and MHC2A maintain the number of myonuclei, whereas MHC2X or MHC2B fibers show loss of myonuclei during normal muscle growth. Both CoS groups displayed smaller CSA and MND size than CTL-AgeM and SHAM-AgeM groups. However, compared with CTL-WtM DIAm fibers, only fibers containing MHC2X or MHC2B displayed reduced CSA and MND size after CoS treatment. Thus little, if any, loss of myonuclei was associated with CoS-induced atrophy of MHC2X or MHC2B DIAm fibers. In summary, MND size does not appear to be regulated during CoS-induced DIAm atrophy.
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands.
authors.forename: A Jeroen
authors.initials: AJ
authors.lastname: Verheul
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Mantilla
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Zhan
authors.forename: Miguel
authors.initials: M
authors.lastname: Bernal
authors.forename: P N Richard
authors.initials: PN
authors.lastname: Dekhuijzen
authors.forename: Gary C
authors.initials: GC
authors.lastname: Sieck
mesh_terms: D000818:Animals; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D003964:Diaphragm / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005938:Glucocorticoids; D018995:Myosin Heavy Chains; D008775:Methylprednisolone