Premium
Antioxidant administration attenuates mechanical ventilation‐induced rat diaphragm muscle atrophy independent of protein kinase B (PKB–Akt) signalling
Author(s) -
McClung J. M.,
Kavazis A. N.,
Whidden M. A.,
DeRuisseau K. C.,
Falk D. J.,
Criswell D. S.,
Powers S. K.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.141119
Subject(s) - protein kinase b , foxo3 , foxo1 , oxidative stress , endocrinology , medicine , trolox , pi3k/akt/mtor pathway , muscle atrophy , chemistry , biology , microbiology and biotechnology , skeletal muscle , signal transduction , biochemistry , antioxidant capacity
Oxidative stress promotes controlled mechanical ventilation (MV)‐induced diaphragmatic atrophy. Nonetheless, the signalling pathways responsible for oxidative stress‐induced muscle atrophy remain unknown. We tested the hypothesis that oxidative stress down‐regulates insulin‐like growth factor‐1–phosphotidylinositol 3‐kinase–protein kinase B serine threonine kinase (IGF‐1–PI3K–Akt) signalling and activates the forkhead box O (FoxO) class of transcription factors in diaphragm fibres during MV‐induced diaphragm inactivity. Sprague–Dawley rats were randomly assigned to one of five experimental groups: (1) control (Con), (2) 6 h of MV, (3) 6 h of MV with infusion of the antioxidant Trolox, (4) 18 h of MV, (5) 18 h of MV with Trolox. Following 6 h and 18 h of MV, diaphragmatic Akt activation decreased in parallel with increased nuclear localization and transcriptional activation of FoxO1 and decreased nuclear localization of FoxO3 and FoxO4, culminating in increased expression of the muscle‐specific ubiquitin ligases, muscle atrophy factor ( MAFbx ) and muscle ring finger‐1 ( MuRF‐1 ). Interestingly, following 18 h of MV, antioxidant administration was associated with attenuation of MV‐induced atrophy in type I, type IIa and type IIb/IIx myofibres. Collectively, these data reveal that the antioxidant Trolox attenuates MV‐induced diaphragmatic atrophy independent of alterations in Akt regulation of FoxO transcription factors and expression of MAFbx or MuRF‐1 . Further, these results also indicate that differential regulation of diaphragmatic IGF‐1–PI3K–Akt signalling exists during the early and late stages of MV.