Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei

Esther E. Dupont-Versteegden, Beau A. Strotman, Cathy M. Gurley, Dana Gaddy, Micheal Knox, James D. Fluckey, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Skeletal muscle atrophy is associated with an increase in apoptosis, and we showed previously that endonuclease G (EndoG) is localized to nuclei following unloading. The goal of this study was to determine whether the onset of apoptosis in response to disuse was consistent with the hypothesis that EndoG is involved in myofiber nuclear loss. Atrophy was induced by hindlimb suspension for 12 h or 1, 2, 4 and 7 days in 6-mo-old rats. Soleus myofiber cross-sectional area decreased significantly by 2 days, whereas muscle mass and muscle-tobody mass ratio decreased by 4 and 7 days, respectively. By contrast, a significant increase in apoptosis, evidenced by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei, occurred as early as 12 h after suspension, preceding the elevation in muscle atrophy F-box gene expression. The early increase in apoptosis appeared to be specific to myofiber nuclei, whereas TUNEL-positive interstitial cells did not become significantly elevated until 2 days after suspension. Furthermore, TUNELpositive myofiber nuclei colocalized with EndoG as early as 12 h after suspension, and no such localization was observed in interstitial cells. Although no significant change in total activated caspase-3, -7, or -12 protein abundance was apparent, activated caspase-3 was expressed in interstitial cells undergoing apoptosis, some of which were endothelial cells. These data indicate that apoptosis is an early, and therefore possibly causative, event in the process of muscle atrophy, and that EndoG nuclear translocation is specific for myofiber nuclear apoptosis, whereas interstitial cells may undergo apoptosis via a more classical, caspase-dependent pathway.

Original languageEnglish
Pages (from-to)R1730-R1740
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume291
Issue number6
DOIs
StatePublished - 2006

Keywords

  • Caspase
  • Endonuclease G
  • Endothelial cells
  • Hindlimb suspension
  • Muscle atrophy F-box

ASJC Scopus subject areas

  • General Medicine

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