title: Antimuscle atrophy effect of nicotine targets muscle satellite cells partly through an α7 nicotinic receptor in a murine hindlimb ischemia model.
abstract: We have recently identified that donepezil, an anti-Alzheimer drug, accelerates angiogenesis in a murine hindlimb ischemia (HLI) model. However, the precise mechanisms are yet to be fully elucidated, particularly whether the effects are derived from endothelial cells alone or from other nonvascular cells. Further investigation of the HLI model revealed that nicotine accelerated angiogenesis by activation of vascular endothelial cell growth factor (VEGF) synthesis through nicotinic receptors in myogenic cells, that is, satellite cells, in vivo and upregulated the expression of angiogenic factors, for example, VEGF and fibroblast growth factor 2, in vitro. As a result, nicotine prevented skeletal muscle from ischemia-induced muscle atrophy and upregulated myosin heavy chain expression in vitro. The in vivo anti-atrophy effect of nicotine on muscle was also observed in galantamine, another anti-Alzheimer drug, playing as an allosteric potentiating ligand. Such effects of nicotine were attenuated in α7 nicotinic receptor knockout mice. In contrast, PNU282987, an α7 nicotinic receptor agonist, comparably salvaged skeletal muscle, which was affected by HLI. These results suggest that cholinergic signals also target myogenic cells and have inhibiting roles in muscle loss by ischemia-induced muscle atrophy.
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo, Japan. Electronic address: k12417853@nms.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Oikawa
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Iketani
authors.affiliation: Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurabayashi
authors.affiliation: Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kurabayashi
authors.affiliation: Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply; D009133:Muscular Atrophy / Q000517:prevention & control*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D018722:Nicotinic Agonists; C498513:PNU-282987; D042461:Vascular Endothelial Growth Factor A; D064569:alpha7 Nicotinic Acetylcholine Receptor; C467480:vascular endothelial growth factor A, mouse; D009538:Nicotine