Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients
| Autor: | Michael J. Tisdale, Helen L. Eley, Richard J E Skipworth, K.C.H. Fearon, D A C Deans |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male muscle atrophy Cancer Research medicine.medical_specialty Cachexia viruses Eukaryotic Initiation Factor-2 eIF2α macromolecular substances Adenocarcinoma Protein degradation Biology Models Biological environment and public health eIF-2 Kinase Internal medicine Weight Loss Myosin medicine Humans Phosphorylation Muscle Skeletal Molecular Diagnostics Aged Gastrointestinal Neoplasms Aged 80 and over eIF2 Autophosphorylation Skeletal muscle PKR Middle Aged Protein kinase R Muscle atrophy Up-Regulation Muscular Atrophy enzymes and coenzymes (carbohydrates) Endocrinology medicine.anatomical_structure Oncology Female medicine.symptom cancer patients p70S6k |
| Zdroj: | Eley, H L, Skipworth, R J E, Deans, D A C, Fearon, K C H & Tisdale, M J 2008, ' Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients ', British Journal of Cancer, vol. 98, no. 2, pp. 443-449 . https://doi.org/10.1038/sj.bjc.6604150 British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6604150 |
| Popis: | Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the alpha-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2alpha have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2alpha were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2alpha (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2alpha. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2alpha (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients. |
| Databáze: | OpenAIRE |
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