Prion protein expression in muscle cells and toxicity of a prion protein fragment.
The prion protein (PrP) is a cell surface glycoprotein normally associated with neurones. Expression of the prion protein in cultured mouse myoblasts and myotubes suggests that the prion protein may play a physiological role in skeletal muscle. When myotubes differentiate from myoblasts prion protein expression is upregulated. Accompanying this increase is an upregulation of Cu/Zn superoxide dismutase (SOD-1) in myotubes. Muscle cells derived from mice deficient in cellular PrP (PrPc) show little increase in SOD-1 after differentiation from myoblasts to myotubes. Myoblasts and myotubes are resistant to the toxicity of a neurotoxic prion protein peptide (PrP106-126). However, in the presence of murine microglia, PrP106-126 causes a reduction in cell number. This effect is greater on myotubes than myoblasts. Even in the presence of microglia PrP106-126 is not toxic to muscle cells derived from PrP-deficient mice. Our results suggest that PrPc expression is associated with regulation of cellular resistance to oxidative stress in skeletal muscle.
Brown
D R
DR
Institut für Neuropathologie, Universität Göttingen, Germany.
Schmidt
B
B
Groschup
M H
MH
Kretzschmar
H A
HA
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000633:toxicity*; D011328:Prions / Q000096:biosynthesis* / Q000633:toxicity*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D013482:Superoxide Dismutase