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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles

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Author(s):
Graca, Flavia A. [1] ; Goncalves, Dawit A. P. [1] ; Silveira, Wilian A. [1] ; Lira, Eduardo C. [1] ; Chaves, Valeria Ernestania [2] ; Zanon, Neusa M. [1] ; Garofalo, Maria Antonieta R. [1] ; Kettelhut, Isis C. [1, 3] ; Navegantes, Luiz C. C. [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Dept Physiol, Ribeirao Preto Med Sch, Sao Paulo - Brazil
[2] Univ Fed Sao Joao del Rei, Lab Physiol & Pharmacol, Divinopolis, MG - Brazil
[3] Univ Sao Paulo, Dept Biochem Immunol, Ribeirao Preto Med Sch, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 305, n. 12, p. E1483-E1494, DEC 2013.
Web of Science Citations: 9
Abstract

The physiological role of epinephrine in the regulation of skeletal muscle protein metabolism under fasting is unknown. We examined the effects of plasma epinephrine depletion, induced by adrenodemedullation (ADMX), on muscle protein metabolism in fed and 2-day-fasted rats. In fed rats, ADMX for 10 days reduced muscle mass, the cross-sectional area of extensor digitorum longus (EDL) muscle fibers, and the phosphorylation levels of Akt. In addition, ADMX led to a compensatory increase in muscle sympathetic activity, as estimated by the rate of norepinephrine turnover; this increase was accompanied by high rates of muscle protein synthesis. In fasted rats, ADMX exacerbated fasting-induced proteolysis in EDL but did not affect the low rates of protein synthesis. Accordingly, ADMX activated lysosomal proteolysis and further increased the activity of the ubiquitin (Ub)-proteasome system (UPS). Moreover, expression of the atrophy-related Ub ligases atrogin-1 and MuRF1 and the autophagy-related genes LC3b and GABARAPl1 were upregulated in EDL muscles from ADMX-fasted rats compared with sham-fasted rats, and ADMX reduced cAMP levels and increased fasting-induced Akt dephosphorylation. Unlike that observed for EDL muscles, soleus muscle proteolysis and Akt phosphorylation levels were not affected by ADMX. In isolated EDL, epinephrine reduced the basal UPS activity and suppressed overall proteolysis and atrogin-1 and MuRF1 induction following fasting. These data suggest that epinephrine released from the adrenal medulla inhibits fasting-induced protein breakdown in fast-twitch skeletal muscles, and these antiproteolytic effects on the UPS and lysosomal system are apparently mediated through a cAMP-Akt-dependent pathway, which suppresses ubiquitination and autophagy. (AU)

FAPESP's process: 08/06694-6 - Neural control of protein metabolism
Grantee:Isis Do Carmo Kettelhut
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/24524-6 - Control of muscle mass by cAMP signaling pathway
Grantee:Isis Do Carmo Kettelhut
Support type: Research Projects - Thematic Grants
FAPESP's process: 09/07584-2 - Role of signaling pathways Akt/Foxo and MEK/ERK on anti-atrophic effect induced by adrenoceptors-B2 in rat skeletal muscle
Grantee:Dawit Albieiro Pinheiro Gonçalves
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 10/11015-0 - Intracellular mechanisms involved in anticatabolic effect of the epinephrine in skeletal muscle of fasted rats
Grantee:Flávia Aparecida Graça
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 10/11083-6 - ROLE OF EPAC IN CONTROL OF PROTEIN METABOLISM IN SKELETAL MUSCLE
Grantee:Wilian de Assis Silveira
Support type: Scholarships in Brazil - Doctorate