Β2‐adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy. Issue 4 (28th February 2020)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: FASEB journal. Volume 34:Issue 4(2020)
• Page Start: 5628
• Page End: 5641
• Publication Date: 2020-02-28
• Subjects: G protein‐coupled proteins -- protein quality control -- skeletal muscle diseases -- therapy; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201902305R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: β2 ‐adrenoceptor agonists improve autophagy and re‐establish proteostasis in cardiac cells; therefore, suggesting autophagy as a downstream effector of β2 ‐adrenoceptor signaling pathway. Here, we used the pharmacological and genetic tools to determine the autophagy effect of sustained β2 ‐adrenoceptor activation in rodents with neurogenic myopathy, which display impaired skeletal muscle autophagic flux. Sustained β2 ‐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 β2 ‐adrenoceptor activation on the skeletal muscle proteostasis and contractility properties in neurogenic myopathy. Further supporting an autophagy mechanism for β2 ‐adrenoceptor activation, skeletal muscle‐specific deletion of ATG7 blunts the beneficial effects of β2 ‐adrenoceptor on skeletal muscle proteostasis and contractility properties in neurogenic myopathy in mice. These findings suggest autophagy as a critical downstream effector of β2 ‐adrenoceptor signaling pathway in skeletal muscle.