In the present study, the BCAAs (branched-chain amino acids) leucine and valine caused a significant suppression in the loss of body weight in mice bearing a cachexia-inducing tumour (MAC16), producing a significant increase in skeletal muscle wet weight, through an increase in protein synthesis and a decrease in degradation. Leucine attenuated the increased phosphorylation of PKR (double-stranded-RNA-dependent protein kinase) and eIF2α (eukaryotic initiation factor 2α) in skeletal muscle of mice bearing the MAC16 tumour, due to an increased expression of PP1 (protein phosphatase 1). Weight loss in mice bearing the MAC16 tumour was associated with an increased amount of eIF4E bound to its binding protein 4E-BP1 (eIF4E-binding protein 1), and a progressive decrease in the active eIF4G–eIF4E complex due to hypophosphorylation of 4E-BP1. This may be due to a reduction in the phosphorylation of mTOR (mammalian target of rapamycin), which may also be responsible for the decreased phosphorylation of p70S6k (70 kDa ribosomal S6 kinase). There was also a 5-fold increase in the phosphorylation of eEF2 (eukaryotic elongation factor 2), which would also decrease protein synthesis through a decrease in translation elongation. Treatment with leucine increased phosphorylation of mTOR and p70S6k, caused hyperphosphorylation of 4E-BP1, reduced the amount of 4E-BP1 associated with eIF4E and caused an increase in the eIF4G–eIF4E complex, together with a reduction in phosphorylation of eEF2. These changes would be expected to increase protein synthesis, whereas a reduction in the activation of PKR would be expected to attenuate the increased protein degradation.
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Research Article|
September 12 2007
Effect of branched-chain amino acids on muscle atrophy in cancer cachexia Available to Purchase
Helen L. Eley;
Helen L. Eley
1Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
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Steven T. Russell;
Steven T. Russell
1Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
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Michael J. Tisdale
Michael J. Tisdale
1
1Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 15 2007
Revision Received:
June 25 2007
Accepted:
July 10 2007
Accepted Manuscript online:
July 10 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 407 (1): 113–120.
Article history
Received:
May 15 2007
Revision Received:
June 25 2007
Accepted:
July 10 2007
Accepted Manuscript online:
July 10 2007
Citation
Helen L. Eley, Steven T. Russell, Michael J. Tisdale; Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem J 1 October 2007; 407 (1): 113–120. doi: https://doi.org/10.1042/BJ20070651
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