Distinct signal transductions in fast- and slow- twitch muscles upon denervation

Physiological Reports
Hongbo Gao, Yi-Fan Li

Abstract

Denervation induces skeletal muscle atrophy, which primarily impairs oxidative slow twitch fibers. The underlying mechanism of this phenomenon, however, remains to be addressed. We hypothesize that denervation-induced fiber-specific atrophy may result from the distinct activities of different signaling pathways that are involved in protein synthesis and degradation in fast- and slow-twitch fibers. In this study, 1-month-old male mice were subjected to unilateral sciatic denervation for 4 days. Fast-twitch muscle extensor digitorum longus (EDL) and slow-twitch muscle soleus were collected from the denervated side and the control side of hind limbs. Total and phosphorylated protein levels of key factors of major signaling pathways in these tissues were determined using western blot assay. Our data showed that total AKT and FoxO3 protein levels were upregulated in denervated muscles as compared with control sides. Phosphorylation of AKT and FoxO3 were proportionally enhanced in denervated EDL but not soleus, indicating AKT activation drives phosphorylation of FoxO3 in EDL but not in soleus upon denervation. As a result, FoxO3-targeted atrogenes MurF1 and Atrogin1 protein abundances were reduced in denervated EDL but not altered in...Continue Reading

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Citations

May 28, 2019·Animal Science Journal = Nihon Chikusan Gakkaihō·Yusuke KomiyaKeizo Arihara
Nov 15, 2018·International Journal of Molecular Sciences·Natalia A VilchinskayaBoris S Shenkman
Jul 20, 2019·Nature Communications·Perrine CastetsMarkus A Rüegg
Oct 14, 2018·International Journal of Molecular Sciences·David M Thomson

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