Total 4EBP1 Is Elevated in Liver of Rats in Response to Low Sulfur Amino Acid Intake.
Total 4EBP1 Is Elevated in Liver of Rats in Response to Low Sulfur Amino Acid Intake.
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DOI：
10.1155/2013/864757
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Stipanuk MH
中科院分区：
文献类型：
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作者：
Sikalidis AK;Mazor KM;Kang M;Liu H;Stipanuk MH
已知翻译起始受真核起始因子4E （eIF4E）与结合蛋白（4EBPs）结合的调控，有证据表明氨基酸剥夺和其他细胞应激可上调4EBP1的表达。为了探究限制必需氨基酸的饮食是否会诱导体内4EBP1的表达，我们给大鼠喂食不同蛋氨酸和胱氨酸含量的饮食7天，测定4EBP1 mRNA和蛋白水平以及4EBP1的磷酸化状态。在严重缺乏含硫氨基酸（0.23%或0.11%蛋氨酸不含胱氨酸）的大鼠肝脏中，总4EBP1 mRNA和蛋白质丰度增加，但在摄入较少限制的含硫氨基酸（0.11%蛋氨酸加0.35%胱氨酸）但同样限制总饮食摄入量（对照组的53%至62%）的动物肝脏中没有增加。饲粮中缺乏硫氨基酸的大鼠肝脏中4EBP1结合活性（α + β形式）的数量增加，而饮食处理不影响4EBP1的过度磷酸化。结果表明，在氨基酸缺乏状态下，在研究削弱蛋白质合成的机制时，应该考虑4EBP1总表达的变化。
Translation initiation is known to be regulated by the binding of eukaryotic initiation factor 4E (eIF4E) by binding proteins (4EBPs), and there is evidence that amino acid deprivation and other cellular stresses upregulate 4EBP1 expression. To pursue the question of whether diets limited in an essential amino acid lead to induction of 4EBP1 expression in vivo, diets that varied in methionine and cystine content were fed to rats for 7 days, and 4EBP1 mRNA and protein levels and 4EBP1 phosphorylation state were determined. Total 4EBP1 mRNA and protein abundance increased in liver of rats with severely deficient intakes of sulfur amino acids (0.23% or 0.11% methionine without cystine) but not in animals with a less restricted intake of sulfur amino acids (0.11% methionine plus 0.35% cystine) but a similarly restricted intake of total diet (53 to 62% of control). The amount of 4EBP1 binding activity (α + β forms) was elevated in liver of rats fed sulfur amino acid-deficient diets, whereas the hyperphosphorylation of 4EBP1 was not affected by dietary treatment. Results suggest that changes in total 4EBP1 expression should be considered when examining mechanisms that attenuate protein synthesis during amino acid deficiency states.