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Running Title: Diaphragm muscle signaling with malnutrition ADDRESS CORRESPONDENCE TO:

By  and Michael I. LewisSue C. Bodine, Nader Kamangar, Xuan Xu, Xiaoyu Da, Mario Fournier and Michael I. Lewis


Copyright © 2006 by the American Physiological Society. JAP-01233-2005.R1 The aim of this study was to evaluate the effect of nutritional deprivation (ND) on signal transduction pathways impinging on the translational apparatus in the diaphragm muscle. Male rats were divided into 2 groups: 1) ND (20 % of usual food intake) for 4 days with water provided at libitum; and 2) free-eating controls (CTL). Total protein and RNA were extracted from the diaphragm. IGF-I mRNA was analyzed by RT-PCR. Protein analyses of key cytoplasmic proteins for 3 signaling pathways deemed important in influencing protein turnover were performed by Western blot. Body weight was reduced 30 % with ND while CTL gained 17%. Diaphragm mass decreased by 29 % with ND. Muscle IGF-I mRNA abundance was reduced by 63 % in ND animals. PI3 kinase/Akt/mTOR pathway: ND resulted in a 55 % reduction in phosphorylated (Ser 473) Akt. The phosphorylation of mTOR at Ser 2448 was reduced by 85 % with ND. Downstream effectors important in translation initiation were also impacted by ND. Phosphorylated (Thr 389) p70 S6K was significantly reduced (35%) with ND. The translational repressor 4E-BP1 was also significantl

Year: 2013
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