Effects of clenbuterol and cyclosporin A on the myosin heavy chain mRNA level and the muscle mass in rat masseter.
To gain more insight into the molecular mechanism of muscle growth and fiber-type transformations, we analyzed the effects of beta(2)-adrenergic agonist clenbuterol (CB) and/or cyclosporin A (CsA), a potent inhibitor of calcineurin (CaN), on the muscle mass as well as on the mRNA levels of myosin heavy chains (MHC I, IIa, IId/x, IIb), using a real-time RT-PCR with specific primers in rat masseter. In comparison with control, the CB treatment significantly decreased the MHC I mRNA level (p < 0.01), but increased the MHC IId/x mRNA level (p < 0.01), and the CsA treatment significantly decreased the MHC I mRNA level (p < 0.05) in association with the significant decrease in MHC IIb mRNA level (p < 0.05). The CB+CsA treatment significantly decreased the levels of MHC I (p < 0.01) and IIa mRNAs (p < 0.05), but increased the MHC IId/x mRNA level (p < 0.001) in association with a significant decrease in MHC IIb mRNA level (p < 0.01), in comparison with control. The masseter muscle mass was significantly (p < 0.001) increased by either the CB or the CB + CsA treatment, but decreased with the CsA treatment (p < 0.01). These results suggest that in rat masseter muscle, CB has an anabolic action accompanying MHC mRNA I IIa IId/x sequence transition independently of CaN-signaling pathways, and CaN is involved in the type I fiber gene expression and the muscle mass maintenance of type IIb fiber.
Arai
Chihiro
C
Department of Orthodontics, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
Ohnuki
Yoshiki
Y
Umeki
Daisuke
D
Hirashita
Ayao
A
Saeki
Yasutake
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D002976:Clenbuterol / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008406:Masseter Muscle / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
D000318:Adrenergic beta-Agonists; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016572:Cyclosporine; D019703:Calcineurin; D018995:Myosin Heavy Chains; D002976:Clenbuterol