Hyperoxia alters the expression and phosphorylation of multiple factors regulating translation initiation.
Hyperoxia alters the expression and phosphorylation of multiple factors regulating translation initiation.
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高氧会改变调节翻译起始的多种因子的表达和磷酸化。
DOI：
10.1152/ajplung.00127.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Barchowsky,Aaron
中科院分区：
文献类型：
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作者：
Shenberger,JeffreyS;Myers,JenniferL;Zimmer,StephenG;Powell,RichardJ;Barchowsky,Aaron
高氧具有细胞毒性，会抑制许多细胞代谢功能，包括蛋白质合成。翻译控制主要在起始过程中通过两种机制发挥作用：1) 通过封堵帽结合蛋白、真核起始因子 (eIF) 4E 和抑制性 4E 结合蛋白 (4E-BP)，抑制翻译起始复合物的形成； 2) 通过防止 eIF2-GTP-tRNA\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{\mathrm{Met}}\) \end{document} 形成和 eIF2B 活动磷酸化 eIF2α。在本报告中，将人肺成纤维细胞暴露于 95% O2 中，6 小时后胸苷掺入 DNA 的量减少，12 小时开始亮氨酸掺入蛋白质的量减少。 DNA 和蛋白质合成的减少伴随着 eIF4E 蛋白磷酸化的增加和 4E-BP1 磷酸化的减少。 24 小时，高氧使 4E-BP1 磷酸化转变为磷酸化程度较低的异构体，增加 eIF4E 表达，并增加 eIF4E 与 4E-BP1 的关联。虽然高氧并没有改变 eIF2α 的表达，但它增加了 Ser51 的磷酸化，但直到 48 小时才出现。此外，eIF2α的激活并不伴随着应激颗粒的形成。这些发现表明，高氧通过增加 eIF4E 磷酸化和增强 4E-BP1 对 eIF4E 的亲和力来减少蛋白质合成。
Hyperoxia is cytotoxic and depresses many cellular metabolic functions including protein synthesis. Translational control is exerted primarily during initiation by two mechanisms:1) through inhibition of translation initiation complex formation via sequestration of the cap-binding protein, eukaryotic initiation factor (eIF) 4E, with inhibitory 4E-binding proteins (4E-BP); and2) by prevention of eIF2-GTP-tRNA\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{\mathrm{Met}}\) \end{document} formation and eIF2B activity by phosphorylated eIF2α. In this report, exposure of human lung fibroblasts to 95% O2decreased the incorporation of thymidine into DNA at 6 h and the incorporation of leucine into protein beginning at 12 h. The reductions in DNA and protein synthesis were accompanied by increased phosphorylation of eIF4E protein and reduced phosphorylation of 4E-BP1. At 24 h, hyperoxia shifted 4E-BP1 phosphorylation to lesser-phosphorylated isoforms, increased eIF4E expression, and increased the association of eIF4E with 4E-BP1. Although hyperoxia did not change eIF2α expression, it increased its phosphorylation at Ser51, but not until 48 h. In addition, the activation of eIF2α was not accompanied by the formation of stress granules. These findings suggest that hyperoxia diminishes protein synthesis by increasing eIF4E phosphorylation and enhancing the affinity of 4E-BP1 for eIF4E.