ß2-Adrenergic Agonist Suppresses Foxo Transcriptional Activity by Regulating Foxo1 Phosphorylation but not Acetylation in Skeletal Muscle

This study was undertaken to identify: 1) whether s2-adrenergic agonist (BA) suppresses Foxo transcriptional activity and the expression of atrophy-related genes (atrogenes) in skeletal muscles and 2) which post-translational modification [i.e., phosphorylation (p) and acetylation (ac)] is related to the inhibition of Foxo1. For that, we examined Formoterol (FOR), a newer generation of BA, effects on the levels of p-Foxo1, ac-Foxo1, p-Akt and p-CREB, a canonical target of BA signaling, by immunoblotting, the activity of Foxo by reporter luciferase assay and the mRNA levels of atrogenes (Atrogin-1, MuRF1 and Gabarapl1) by qPCR in muscles from 2-d fasted rodents. Fasting reduced p-Akt (~80%) and p-Foxo1 (30%) and increased Foxo activity (~15-fold) and atrogenes expression (~7-fold). Thirty min after an injection, FOR in vivo (300 μg.kg-1) caused an elevation in p-Akt (~10-fold), p-Foxo1 (2-fold) and p-CREB (2-fold). At 4h, FOR reduced Foxo activity (~40%) and atrogenes mRNAs (~40%). In isolated muscles from...