1. Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells
- Author
-
Federica Chianale, Santina Cutrupi, Corrado Ghè, Gianluca Baldanzi, Nicoletta Filigheddu, Tiziana Crepaldi, Nicola Surico, Miriam Cappelli, Sara Traini, Fabiola Sinigaglia, Giampiero Muccioli, Viola F. Gnocchi, Elisa Arnoletti, Riccardo Taulli, Carola Ponzetto, Paolo E. Porporato, Alberto Fubini, Andrea Graziani, Marco Coscia, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Filigheddu, N, Gnocchi, Vf, Coscia, M, Cappelli, M, PORPORATO PAOLO, E, Taulli, R, Traini, S, Baldanzi, Gl, Chianale, F, Cutrupi, S, Arnoletti, E, Gh, C, Fubini, A, Surico, N, Sinigaglia, F, Ponzetto, P, Muccioli, Gp, Crepaldi, T, and Graziani, Andrea
- Subjects
medicine.medical_specialty ,Cellular differentiation ,media_common.quotation_subject ,Peptide Hormones ,Growth hormone secretagogue receptor ,Muscle Fibers, Skeletal ,Biology ,Peptide hormone ,p38 Mitogen-Activated Protein Kinases ,Receptors, G-Protein-Coupled ,Cell Fusion ,Mice ,Internal medicine ,medicine ,skeletal muscle differentiation ,Animals ,RNA, Messenger ,Receptor ,Ghrelin ,Muscle, Skeletal ,Receptors, Ghrelin ,Molecular Biology ,media_common ,Cell Proliferation ,Binding Sites ,Myogenesis ,digestive, oral, and skin physiology ,Appetite ,Cell Differentiation ,Cell Biology ,DNA ,Articles ,Culture Media ,Enzyme Activation ,Endocrinology ,Gene Expression Regulation ,C2C12 ,hormones, hormone substitutes, and hormone antagonists ,Biomarkers - Abstract
Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. Inhere we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.
- Published
- 2007