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

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...

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Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2014-07, Vol.164 (1), p.32-45
Main Authors: Kakinuma, Yoshihiko, Noguchi, Tatsuya, Okazaki, Kayo, Oikawa, Shino, Iketani, Mitsue, Kurabayashi, Atsushi, Furihata, Mutsuo, Sato, Takayuki
Format: Article
Language:English
Subjects:
alpha7 Nicotinic Acetylcholine Receptor - antagonists & inhibitors
alpha7 Nicotinic Acetylcholine Receptor - genetics
alpha7 Nicotinic Acetylcholine Receptor - metabolism
Animals
Benzamides - pharmacology
Bridged Bicyclo Compounds - pharmacology
Cells, Cultured
Gene Expression Regulation - physiology
Hindlimb - blood supply
Internal Medicine
Ischemia - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal - blood supply
Muscular Atrophy - prevention & control
Nicotine - pharmacology
Nicotinic Agonists - pharmacology
Satellite Cells, Skeletal Muscle - drug effects
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
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Summary: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.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2014.02.005