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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.)

cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice

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Author(s):
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Silveira, Wilian A. [1, 2] ; Goncalves, Dawit A. [1, 3, 4, 5, 6, 7] ; Machado, Juliano [1, 8] ; Lautherbach, Natalia [1] ; Lustrino, Danilo [1, 9] ; Paula-Gomes, Silvia [5, 6, 10] ; Pereira, Marcelo G. [11, 12] ; Miyabara, Elen H. [11] ; Sandri, Marco [3, 4, 13] ; Kettelhut, Isis C. [1, 5, 6] ; Navegantes, Luiz C. [1]
Total Authors: 11
Affiliation:
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[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Sao Paulo - Brazil
[2] Fed Univ Trifingulo Mineiro UFTM, Inst Biol & Nat Sci, Uberaba - Brazil
[3] Univ Padua, Dept Biomed Sci, Padua - Italy
[4] Venetian Inst Mol Med, Padua - Italy
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem, Sao Paulo - Brazil
[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Immunol, Sao Paulo - Brazil
[7] Fed Univ Minas Gerais UFMG, Dept Phys Educ, Sch Phys Educ Physiotherapy & Occupat Therapy, Belo Horizonte, MG - Brazil
[8] Helmholtz Ctr Munich, Inst Diabet & Canc IDC, Neuherberg - Germany
[9] Univ Fed Sergipe, Dept Physiol, Aracaju - Brazil
[10] Univ Fed Ouro Preto, Inst Exact & Biol Sci, Dept Biol Sci, Ouro Preto - Brazil
[11] Univ Sao Paulo, Dept Anat Inst Biomed Sci, Sao Paulo - Brazil
[12] Univ Sao Paulo, Sch Phys Educ & Sport, Dept Biodynam Human Body Movement, Sao Paulo - Brazil
[13] Univ Padua, Myol Ctr, Padua - Italy
Total Affiliations: 13
Document type: Journal article
Source: FASEB JOURNAL; v. 34, n. 9 AUG 2020.
Web of Science Citations: 0
Abstract

Although we have shown that catecholamines suppress the activity of the Ubiquitin-Proteasome System (UPS) and atrophy-related genes expression through a cAMP-dependent manner in skeletal muscle from rodents, the underlying mechanisms remain unclear. Here, we report that a single injection of norepinephrine (NE; 1 mg kg(-1); s.c) attenuated the fasting-induced up-regulation of FoxO-target genes in tibialis anterior (TA) muscles by the stimulation of PKA/CREB and Akt/FoxO1 signaling pathways. In addition, muscle-specific activation of PKA by the overexpression of PKA catalytic subunit (PKAcat) suppressed FoxO reporter activity induced by (1) a wild-type; (2) a non-phosphorylatable; (3) a non-phosphorylatable and non-acetylatable forms of FoxO1 and FoxO3; (4) downregulation of FoxO protein content, and probably by (5) PGC-1 alpha up-regulation. Consistently, the overexpression of the PKAcat inhibitor (PKI) up-regulated FoxO activity and the content of Atrogin-1 and MuRF1, as well as induced muscle fiber atrophy, the latter effect being prevented by the overexpression of a dominant negative (d. n.) form of FoxO (d.n.FoxO). The sustained overexpression of PKAcat induced fiber-type transition toward a smaller, slower, and more oxidative phenotype and improved muscle resistance to fatigue. Taken together, our data provide the first evidence that endogenous PKA activity is required to restrain the basal activity of FoxO and physiologically important to maintain skeletal muscle mass. (AU)

FAPESP's process: 18/10089-2 - Neural, hormonal and nutritional control of autophagy
Grantee:Isis Do Carmo Kettelhut
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/18861-0 - FOXO HYPERACETYLATION AS A MECHANISM OF SUPPRESSION OF ATROPHY GENE PROGRAM INDUCED BY BETA2-ADRENERGIC SIGNALING IN RODENT SKELETAL MUSCLE
Grantee:Dawit Albieiro Pinheiro Gonçalves
Support type: Scholarships in Brazil - Post-Doctorate
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