Premium
Phosphodiesterase‐4 inhibition reduces proteolysis and atrogenes expression in rat skeletal muscles
Author(s) -
Lira Eduardo C.,
Gonçalves Dawit A.P.,
ParreirasESilva Lucas T.,
Za Neusa M.,
Kettelhut Isis C.,
Navegantes Luiz C.C.
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.22066
Subject(s) - rolipram , skeletal muscle , endocrinology , phosphodiesterase , protein kinase b , medicine , phosphorylation , phosphodiesterase 3 , muscle atrophy , protein degradation , ubiquitin , chemistry , ubiquitin ligase , protein kinase a , biology , biochemistry , enzyme , gene
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