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β 2 ‐adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy
Author(s) -
Campos Juliane C.,
Baehr Leslie M.,
Ferreira Nikolas D.,
Bozi Luiz H. M.,
Andres Allen M.,
Ribeiro Márcio A. C.,
Gottlieb Roberta A.,
Bodine Sue C.,
Ferreira Julio C. B.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902305r
Subject(s) - skeletal muscle , autophagy , endocrinology , medicine , proteostasis , myopathy , contractility , myocyte , biology , chemistry , microbiology and biotechnology , apoptosis , biochemistry
β 2 ‐adrenoceptor agonists improve autophagy and re‐establish proteostasis in cardiac cells; therefore, suggesting autophagy as a downstream effector of β 2 ‐adrenoceptor signaling pathway. Here, we used the pharmacological and genetic tools to determine the autophagy effect of sustained β 2 ‐adrenoceptor activation in rodents with neurogenic myopathy, which display impaired skeletal muscle autophagic flux. Sustained β 2 ‐adrenoceptor activation using Formoterol (10 μg kg −1 day −1 ), starting at the onset of neurogenic myopathy, prevents disruption of autophagic flux in skeletal muscle 14 days after sciatic nerve constriction. These changes are followed by reduction of the cytotoxic protein levels and increased skeletal muscle cross‐sectional area and contractility properties. Of interest, sustained administration of Formoterol at lower concentration (1 μg kg −1 day −1 ) induces similar improvements in skeletal muscle autophagic flux and contractility properties in neurogenic myopathy, without affecting the cross‐sectional area. Sustained pharmacological inhibition of autophagy using Chloroquine (50 mg kg −1 day −1 ) abolishes the beneficial effects of β 2 ‐adrenoceptor activation on the skeletal muscle proteostasis and contractility properties in neurogenic myopathy. Further supporting an autophagy mechanism for β 2 ‐adrenoceptor activation, skeletal muscle‐specific deletion of ATG7 blunts the beneficial effects of β 2 ‐adrenoceptor on skeletal muscle proteostasis and contractility properties in neurogenic myopathy in mice. These findings suggest autophagy as a critical downstream effector of β 2 ‐adrenoceptor signaling pathway in skeletal muscle.