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Norepinephrine in vivo restores the low phosphorylation levels of Akt and attenuates the high expression of atrophy‐ and autophagy‐related genes in skeletal muscles of fasted mice
Author(s) -
Silveira Wilian Assis,
Gonçalves Dawit A. P.,
Graça Flávia A.,
Za Neusa M.,
Kettelhut Isis C.,
Navegantes Luiz C. C.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1078.36
Subject(s) - protein kinase b , autophagy , phosphorylation , medicine , atrophy , endocrinology , in vivo , muscle atrophy , skeletal muscle , ubiquitin , biology , chemistry , microbiology and biotechnology , gene , biochemistry , apoptosis , genetics
It is well known that catecholamines inhibit skeletal muscle protein degradation, but the molecular underlying mechanism remains unclear. This study was undertaken to investigate the in vitro and in vivo effects of norepinephrine (NOR) on regulating the ubiquitin‐proteasome (UPS) and autophagic/lysosomal systems. The proteolytic activities were determined by measuring the tyrosine release in rat isolated muscles. The gene expression and levels of Akt phosphorylation were examined by RT‐qPCR and Western blotting analysis, respectively. The addition of NOR to the incubation medium of extensor digitorum longus (EDL) muscles from fed rats reduced the basal UPS activity (21%), the expression of atrophy‐related genes, Atrogin‐1 (64%) and MuRF‐1 (43%), and autophagy‐related genes, LC3b (23%) and GABARAPl1 (23%). In C57/BL6 mice, 1‐d fasting reduced the phosphorylation levels of Akt‐Ser473 and up‐regulated the expression of atrophy‐ and autophagy‐related genes in tibialis muscles. One single injection of NOR reestablished the low levels of p‐Akt and attenuated the high expression of atrogin‐1 (63%), MuRF‐1 (60%) and GABARAPl1 (55%) in fasted mice. These data indicate that NOR attenuates the fasting‐induced expression of atrophy‐ and autophagy‐related genes in skeletal muscles of mice, probably involving activation of Akt signaling pathway. Financial support: FAPESP (10/11083‐6; 08/06694‐6).