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ERK1/2 are possible mediators of the anti‐proteolytic effects of β2‐adrenoceptor/cAMP signaling in skeletal muscle
Author(s) -
Gonçalves Dawit Albieiro Pinheiro,
Silveira Wilian A.,
Graça Flávia A.,
Kettelhut Ísis C.,
Navegantes Luiz Carlos 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.1078.30
Subject(s) - skeletal muscle , medicine , endocrinology , kinase , myogenesis , chemistry , phosphorylation , protein kinase b , signal transduction , biology , biochemistry
The present study was undertaken to identify the role of ERK1/2 kinases in the antiproteolytic effects of β2‐adrenoceptor (β2‐AR)/cAMP signaling in skeletal muscles. For that, we examined the effects of Formoterol (FOR), a newer generation β2‐agonist, on the phosphorylation (p) levels of ERK1/2, cAMP content and the mRNA expression of atrophy‐ (Atrogin‐1, MuRF1 and cathepsin L) and autophagy‐ (LC3b and Gabarapl1) related genes in C2C12 myoblast and myotubes cells and adult skeletal muscles. In C2C12 cells, FOR significantly increased p‐ERK1/2 from 5 to 30 min indicating that these kinases can be directly activated by β2‐AR signaling under basal conditions. Following, gastrocnemius and tibialis anterior muscles from 2‐d fasted C57Bl6/J mice were analyzed after 1, 4, and 12h of a single s.c. injection of FOR (3μg/kg; s.c.) Fasting reduced cAMP content (36%) and p‐ERK1/2 (~40%), effects that were associated with the upregulation (6‐ to 10‐fold) of atrophic and autophagic genes. At 1h, FOR reestablished cAMP levels and p‐ERK1/2 and downregulated (~40%) Gabarapl1 mRNA. At 4h, FOR reduced Atrogin‐1 mRNA to basal levels and MuRF1 and Gabarapl1 mRNAs by ~40% but did not alter LC3b and cathepsin L mRNAs. These data suggest the involvement of ERK1/2 kinases in the anti‐proteolytic effects of β2‐AR/cAMP signaling in skeletal muscle. Supported by CNPq & FAPESP (08/06694‐6, 09/07584‐2).