Prion protein expression and functional importance in skeletal muscle

Jeffrey D. Smith, Jennifer S. Moylan, Brian J. Hardin, Melissa A. Chambers, Steven Estus, Glenn C. Telling, Michael B. Reid

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons. Aims: We hypothesize that PrP deficiency would increase oxidant activity in skeletal muscle and alter redox-sensitive functions, including contraction and glucose uptake. We used real-time polymerase chain reaction and Western blot analysis to measure PrP mRNA and protein in human diaphragm, five murine muscles, and muscle-derived C2C12 cells. Effects of PrP deficiency were tested by comparing PrP-deficient mice versus wild-type mice and morpholino-knockdown versus vehicle-treated myotubes. Oxidant activity (dichlorofluorescin oxidation) and specific force were measured in murine diaphragm fiber bundles. Results: PrP content differs among mouse muscles (gastrocnemius>extensor digitorum longus, EDL>tibialis anterior, TA; soleus>diaphragm) as does glycosylation (di-, mono-, nonglycosylated; gastrocnemius, EDL, TA=60%, 30%, 10%; soleus, 30%, 40%, 30%; diaphragm, 30%, 30%, 40%). PrP is predominantly di-glycosylated in human diaphragm. PrP deficiency decreases body weight (15%) and EDL mass (9%); increases cytosolic oxidant activity (fiber bundles, 36%; C2C12 myotubes, 7%); and depresses specific force (12%) in adult (8-12mos) but not adolescent (2mos) mice. Innovation: This study is the first to directly assess a role of prion protein in skeletal muscle function. Conclusions: PrP content varies among murine skeletal muscles and is essential for maintaining normal redox homeostasis, muscle size, and contractile function in adult animals.

Original languageEnglish
Pages (from-to)2465-2475
Number of pages11
JournalAntioxidants and Redox Signaling
Issue number9
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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