Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells.
Dystrophic skeletal muscle cells from Duchenne muscular dystrophy (DMD) patients and mdx mice exhibit elevated cytosolic Ca2+ concentrations ([Ca2+]c). Pretreatment of mdr myotubes for 6-12 days with creatine (20 mM) decreased the elevation in [Ca2+]c induced by either high extracellular Ca2+ concentrations or hypo-osmotic stress to control levels. 45Ca2+ influx measurements suggest that creatine lowered [Ca2+]c by stimulating sarcoplasmic reticulum Ca2+-ATPase. Creatine pretreatment increased levels of phosphocreatine but not ATP. Furthermore, myotube formation and survival were significantly enhanced by creatine pretreatment. Therefore, creatine supplementation may be useful for treatment of DMD.
Pulido
S M
SM
Pharmacology Group, School of Pharmacy, University of Lausanne, Switzerland.
Passaquin
A C
AC
Leijendekker
W J
WJ
Challet
C
C
Wallimann
T
T
Rüegg
U T
UT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003401:Creatine / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine; D002118:Calcium