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J Appl Physiol (July 2, 2004). doi:10.1152/japplphysiol.00625.2003
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Submitted on June 17, 2003
Accepted on June 11, 2004

INFLUENCE OF CORTICOSTEROIDS ON MYONUCLEAR DOMAIN SIZE IN THE RAT DIAPHRAGM MUSCLE

A. Jeroen Verheul1, Carlos B Mantilla2, Wen-Zhi Zhan3, Miguel Bernal3, P. N. Richard Dekhuijzen1, and Gary C Sieck4*

1 Department of Pulmonary Diseases, University Medical Center NijmegenMayo Medical School, Nijmegen, The Netherlands
2 Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN, USA
3 Department of Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA

* To whom correspondence should be addressed. E-mail: sieck.gary{at}mayo.edu.

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/kg/day (CoS-High; n=8). Age-matched (CTL-AgeM; n=8), sham-operated (SHAMAgeM; 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 vs. CTL-AgeM and SHAM-AgeM groups, and all fibers had reduced MND size. 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 when compared to CTL-AgeM and SHAM-AgeM groups. However, when compared to CTL-WtM DIAm fibers, only fibers containing MHC2X or MHC2B displayed reduced CSA and MND size following 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.




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