title: Myogenic differentiation induces taurine transporter in association with taurine-mediated cytoprotection in skeletal muscles.
abstract: Skeletal muscle homoeostasis is maintained by a variety of cytoprotective mechanisms. Since ablation of the TauT (taurine transporter) gene results in susceptibility to exercise-induced muscle weakness in vivo, it has been suggested that TauT is essential for skeletal muscle function. However, the regulatory mechanisms of TauT expression remain to be elucidated. In the present study, we demonstrated that TauT was up-regulated during myogenesis in C2C12 cells. Treatment with bFGF (basic fibroblast growth factor), which inhibited muscle differentiation, abrogated myogenic induction of TauT. The promoter activities of TauT were up-regulated during muscle differentiation in C2C12 cells. Database analyses identified an MEF2 (myocyte enhancer binding factor 2) consensus sequence at -844 in the rat TauT gene. Truncation of the promoter region containing the MEF2 site significantly reduced the promoter activity, demonstrating the functional importance of the MEF2 site. Electrophoretic mobility-shift assays confirmed that MEF2 bound to the MEF2 consensus sequence and that DNA-protein complex levels were increased during differentiation. Promoter analyses using mutated promoter-reporter plasmids demonstrated that this site was functional. Importantly, transfection with a MyoD expression vector markedly enhanced TauT promoter activity in the (non-myogenic) 10T1/2 cells. Moreover, co-transfection with an MEF2 expression vector augmented MyoD-induced TauT promoter activity, suggesting that MEF2 is required for full activation of TauT expression. Finally, we examined the effects of taurine on myotube atrophy to clarify the biological significance of the up-regulation of TauT, and demonstrated that taurine attenuated muscle atrophy induced by dexamethasone. TauT expression is regulated under the control of the myogenic programme, and we propose that this is the mechanism for taurine-mediated resistance to muscle atrophy.
authors.affiliation: Laboratory of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, 565-0871, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Uozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Tomomi
authors.initials: T
authors.lastname: Mohri
authors.forename: Makiko
authors.initials: M
authors.lastname: Maeda
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fujio
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019610:Cytoprotection / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D013654:Taurine / Q000378:metabolism*; D015854:Up-Regulation; D000099247:Taurine Transporters
chemical_list: D003907:Dexamethasone; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D000099247:Taurine Transporters