| Full text | |
| Author(s): |
Lira, Eduardo C.
[1]
;
Goncalves, Dawit A. P.
[1]
;
Parreiras-E-Silva, Lucas T.
[2]
;
Zanon, Neusa M.
[1]
;
Kettelhut, Isis C.
[2]
;
Navegantes, Luiz C. C.
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | MUSCLE & NERVE; v. 44, n. 3, p. 371-381, 2011. |
| Web of Science Citations: | 11 |
| Abstract | |
Phosphodiesterase (PDE) inhibition reduces skeletal muscle atrophy, but the underlying molecular mechanism remains unclear. We used microdialysis to investigate the effects of different PDE inhibitors on interstitial tyrosine concentration as well as proteolytic activity and atrogenes expression in isolated rat muscle. Rolipram, a PDE-4-selective inhibitor, reduced the interstitial tyrosine concentration and rates of muscle protein degradation. The rolipram-induced muscle cAMP increase was accompanied by a decrease in ubiquitin proteasome system (UPS) activity and atrogin-1 mRNA, a ubiquitin-ligase involved in muscle atrophy. This effect was not associated with Akt phosphorylation but was partially blocked by a protein kinase A inhibitor. Fasting increased atrogin-1, MuRF-1 and LC3b expression, and these effects were markedly suppressed by rolipram. Our data suggest that activation of cAMP signaling by PDE-4 blockade leads to inhibition of UPS activity and atrogenes expression independently of Akt. These findings are important for identifying novel approaches to attenuate muscle atrophy. Muscle Nerve 44: 371-381, 2011 (AU) | |
| FAPESP's process: | 08/06694-6 - Neural control of protein metabolism |
| Grantee: | Isis Do Carmo Kettelhut |
| Support Opportunities: | 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 Opportunities: | Scholarships in Brazil - Doctorate |