title: Extracellular ATP signaling during differentiation of C2C12 skeletal muscle cells: role in proliferation.
abstract: Evidence shows that extracellular ATP signals influence myogenesis, regeneration and physiology of skeletal muscle. Present work was aimed at characterizing the extracellular ATP signaling system of skeletal muscle C2C12 cells during differentiation. We show that mechanical and electrical stimulation produces substantial release of ATP from differentiated myotubes, but not from proliferating myoblasts. Extracellular ATP-hydrolyzing activity is low in myoblasts and high in myotubes, consistent with the increased expression of extracellular enzymes during differentiation. Stimulation of cells with extracellular nucleotides produces substantial Ca(2+) transients, whose amplitude and shape changed during differentiation. Consistently, C2C12 cells express several P2X and P2Y receptors, whose level changes along with maturation stages. Supplementation with either ATP or UTP stimulates proliferation of C2C12 myoblasts, whereas excessive doses were cytotoxic. The data indicate that skeletal muscle development is accompanied by major functional changes in extracellular ATP signaling.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Martinello
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Baldoin
authors.forename: Laura
authors.initials: L
authors.lastname: Morbiato
authors.forename: Maddalena
authors.initials: M
authors.lastname: Paganin
authors.forename: Elena
authors.initials: E
authors.lastname: Tarricone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Schiavo
authors.forename: Elisa
authors.initials: E
authors.lastname: Bianchini
authors.forename: Dorianna
authors.initials: D
authors.lastname: Sandonà
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D000255:Adenosine Triphosphate