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首页> 美国卫生研究院文献>The Journal of Nutrition >Growing Rats Respond to a Sulfur Amino Acid–Deficient Diet by Phosphorylation of the α Subunit of Eukaryotic Initiation Factor 2 Heterotrimeric Complex and Induction of Adaptive Components of the Integrated Stress Response
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Growing Rats Respond to a Sulfur Amino Acid–Deficient Diet by Phosphorylation of the α Subunit of Eukaryotic Initiation Factor 2 Heterotrimeric Complex and Induction of Adaptive Components of the Integrated Stress Response

机译：成长中的大鼠通过真核生物起始因子2异源三聚体复合物的α亚基磷酸化和诱导综合应激反应的适应性成分对硫氨基酸缺乏饮食作出反应

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Mammalian cells respond to various kinds of stress, including nutritional stress, via pathways that are initiated by phosphorylation of the α subunit of the eukaryotic initiation factor 2 complex (eIF2α). Because the models used to study eIF2α-kinase–mediated responses to amino acid deficiency have commonly used media or diets devoid of 1 or more essential amino acids, we asked whether eIF2α-kinase–mediated responses would be induced in animals fed a more typical diet that was not as imbalanced as one in which 1 essential amino acid is totally absent. To answer this question, we fed rats soy protein-based diets that were either adequate or limiting in sulfur-containing amino acids (SAA). Rats fed a SAA-deficient diet (3.4 g methionine equivalents/kg diet) grew more slowly than rats fed the control diet (5.86 g methionine equivalents/kg diet). Analysis of liver from rats fed these diets for 7 d showed that the SAA-deficient rats had higher levels of eIF2α phosphorylation and higher levels of activating transcription factor (ATF) 4, ATF3, asparagine synthetase, solute carrier 7A11, cysteinyl-tRNA synthetase, and cystathionine γ-lyase. On the other hand, components of the integrated stress response (ISR) known to promote apoptosis or translational recovery were not induced. Taken together, our results indicate that rats fed the SAA-deficient diet had a prolonged activation of an eIF2α kinase that leads to upregulation of adaptive components of the ISR.
机译：哺乳动物细胞通过真核起始因子2复合物（eIF2α）的α亚基磷酸化而起始的途径，对各种应激（包括营养应激）作出反应。由于用于研究eIF2α激酶介导的氨基酸缺乏反应的模型已普遍使用缺乏1种或多种必需氨基酸的培养基或饮食，因此我们询问是否会在饲喂更典型饮食的动物中诱发eIF2α激酶介导的反应并没有完全缺少1种必需氨基酸的氨基酸失衡。为了回答这个问题，我们给大鼠喂食了以大豆蛋白为主的日粮，这些日粮中的含硫氨基酸（SAA）足够或有限。饲喂SAA缺乏饮食（3.4克蛋氨酸当量/千克饮食）的大鼠比饲喂对照饮食（5.86克蛋氨酸当量/千克饮食）的大鼠生长更慢。对接受这些饮食喂养7天的大鼠进行的肝脏分析表明，缺乏SAA的大鼠具有更高的eIF2α磷酸化水平和更高的活化转录因子（ATF）4，ATF3，天冬酰胺合成酶，溶质载体7A11，半胱氨酰-tRNA合成酶，和胱硫醚γ-裂解酶。另一方面，没有诱导已知的促进细胞凋亡或翻译恢复的整合应激反应（ISR）的组件。两者合计，我们的结果表明，喂养SAA缺乏饮食的大鼠的eIF2α激酶的激活时间延长，从而导致ISR的适应性成分上调。

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