title: Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.
abstract: The molecular mechanisms controlling beta-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.forename: C
authors.initials: C
authors.lastname: Zeng
authors.forename: A
authors.initials: A
authors.lastname: Ricome
authors.forename: K M
authors.initials: KM
authors.lastname: Hannon
authors.forename: A L
authors.initials: AL
authors.lastname: Grant
authors.forename: D E
authors.initials: DE
authors.lastname: Gerrard
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002976:Clenbuterol; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054638:Dual Specificity Phosphatase 1; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006984:Hypertrophy; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D000318:Adrenergic beta-Agonists; D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; D007545:Isoproterenol; D002976:Clenbuterol