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Transl Res. 2014 Jul;164(1):32-45. doi: 10.1016/j.trsl.2014.02.005. Epub 2014 Apr 24.

Antimuscle atrophy effect of nicotine targets muscle satellite cells partly through an α7 nicotinic receptor in a murine hindlimb ischemia model.

Author information

1
Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo, Japan. Electronic address: k12417853@nms.ac.jp.
2
Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan.
3
Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo, Japan.
4
Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan.

Erratum in

  • Transl Res. 2014 Dec;164(6):515. Kurabayashi, Mutsumi [corrected to Kurabayashi, Atsushi].

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.

PMID:
24811002
DOI:
10.1016/j.trsl.2014.02.005
[Indexed for MEDLINE]
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