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.
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.
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DOI：
10.1038/sj.bjc.6604150
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发表时间：
2008-01-29
影响因子：
8.8
通讯作者：
Tisdale, M. J.
中科院分区：
文献类型：
--
作者：
Eley, H. L.;Skipworth, R. J. E.;Deans, D. A. C.;Fearon, K. C. H.;Tisdale, M. J.
以往的研究表明，双链RNA依赖的蛋白激酶的激活(自磷酸化)可以刺激蛋白质的降解，并通过α亚基上的翻译起始因子2(EIF2)的磷酸化来抑制蛋白质的合成。为了了解这些介质是否在癌症患者肌肉萎缩中起重要作用，我们测定了体重减轻的食道癌患者腹直肌中蛋白酪氨酸激酶受体和eIF2α的磷酸型水平，并与健康对照组进行了比较。肿瘤患者肌肉中磷酸化PKR和磷酸化eIF2α水平均显著升高，且二者呈线性关系(相关系数0.76，P=0.005)。这表明PKR的磷酸化导致了eIF2α的磷酸化。肌球蛋白表达水平与eIF2α的磷酸化程度呈线性关系(相关系数0.77，P=0.004)。这些结果表明，PKR的磷酸化可能是癌症患者肌肉萎缩的重要启动因素。
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 α-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2α 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 eIF2α 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 eIF2α (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2α. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2α (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.
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通过抑制DSRNA依赖性蛋白激酶，在恶病质鼠模型中肌肉萎缩的衰减。
影响因子：
8.8
作者：
Eley, H L;Russell, S T;Tisdale, M J
通讯作者：
Tisdale, M J
影响因子：
15.9
作者：
Acharyya, S;Ladner, KJ;Guttridge, DC
通讯作者：
Guttridge, DC
影响因子：
11.4
作者：
CHONG, KL;FENG, L;WILLIAMS, BRG
通讯作者：
WILLIAMS, BRG
DOI：
10.1016/s1357-2725(96)00169-0
发表时间：
1997-07-01
影响因子：
4
作者：
Clemens, MJ
通讯作者：
Clemens, MJ
影响因子：
4.8
作者：
Russell, ST;Wyke, SM;Tisdale, MJ
通讯作者：
Tisdale, MJ