TY - JOUR
T1 - Prion protein expression and functional importance in skeletal muscle
AU - Smith, Jeffrey D.
AU - Moylan, Jennifer S.
AU - Hardin, Brian J.
AU - Chambers, Melissa A.
AU - Estus, Steven
AU - Telling, Glenn C.
AU - Reid, Michael B.
PY - 2011/11/1
Y1 - 2011/11/1
N2 - 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.
AB - 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.
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U2 - 10.1089/ars.2011.3945
DO - 10.1089/ars.2011.3945
M3 - Article
C2 - 21453198
AN - SCOPUS:80052995726
SN - 1523-0864
VL - 15
SP - 2465
EP - 2475
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 9
ER -