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This Article Full Text Full Text (PDF) All Versions of this Article: 585/1/203    most recent jphysiol.2007.141119v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McClung, J. M. Articles by Powers, S. K. Search for Related Content PubMed PubMed Citation Articles by McClung, J. M. Articles by Powers, S. K. Related Collections Respiratory

¹ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA

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.

(Received 20 July 2007; accepted after revision 27 September 2007; first published online 4 October 2007)
Corresponding author J. M. McClung: Department of Applied Physiology and Kinesiology, University of Florida, Room 25 Florida Gym, Gainesville, FL 32611, USA. Email: mmcclung{at}hhp.ufl.edu

This article has been cited by other articles:

				J. M. McClung, M. A. Whidden, A. N. Kavazis, D. J. Falk, K. C. DeRuisseau, and S. K. Powers Redox regulation of diaphragm proteolysis during mechanical ventilation Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1608 - R1617. [Abstract] [Full Text] [PDF]

				T. Barker and M. G. Traber Reply from Tyler Barker and Maret G. Traber J. Physiol., January 1, 2008; 586(1): 309 - 310. [Full Text] [PDF]