The effect of denervation on protein synthesis and degradation in adult rat diaphragm muscle

Heather M. Argadine, Nathan J. Hellyer, Carlos B. Mantilla, Wen Zhi Zhan, Gary C. Sieck

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Previous studies showed that unilateral denervation (DNV) of the rat diaphragm muscle (DIAm) results in loss of myosin heavy chain protein by 1 day after DNV. We hypothesize that DNV decreases net protein balance as a result of activation of the ubiquitin-proteasome pathway. In DIAm strips, protein synthesis was measured by incorporation of 3H-Tyr, and protein degradation was measured by Tyr release at 1, 3, 5, 7, and 14 days after DNV. Total protein ubiquitination, caspase-3 expression/activity, and actin fragmentation were analyzed by Western analysis. We found that, at 3 days after DNV, protein synthesis increased by 77% relative to sham controls. Protein synthesis remained elevated at 5 (85%), 7 (53%), and 14 days (123%) after DNV. At 5 days after DNV, protein degradation increased by 43% relative to sham controls and remained elevated at 7 (49%) and 14 days (74%) after DNV. Thus, by 5 days after DNV, net protein balance decreased by 43% compared with sham controls and was decreased compared with sham at 7 (49%) and 14 days (72%) after DNV. Protein ubiquitination increased at 5 days after DNV and remained elevated. DNV had no effect on caspase-3 activity or actin fragmentation, suggesting that the ubiquitin-proteasome pathway rather than caspase-3 activation is important in the DIAm response to DNV. Early loss of contractile proteins, such as myosin heavy chain, is likely the result of selective protein degradation rather than generalized protein breakdown. Future studies should evaluate this selective effect of DNV.

Original languageEnglish (US)
Pages (from-to)438-444
Number of pages7
JournalJournal of applied physiology
Volume107
Issue number2
DOIs
StatePublished - Aug 2009

Keywords

  • Innervation
  • Protein balance
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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