title: Prion protein expression and functional importance in skeletal muscle.
abstract: Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons.
  
  
  OBJECTIVE
  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 (8-12 mos) but not adolescent (2 mos) mice.
  
  
  METHODS
  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.
authors: Department of Physiology, University of Kentucky, Lexington, 40536, USA.
authors: Jeffrey D
authors: JD
authors: Smith
authors: Jennifer S
authors: JS
authors: Moylan
authors: Brian J
authors: BJ
authors: Hardin
authors: Melissa A
authors: MA
authors: Chambers
authors: Steven
authors: S
authors: Estus
authors: Glenn C
authors: GC
authors: Telling
authors: Michael B
authors: MB
authors: Reid
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003964:Diaphragm / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions