Naked mole rats (NMRs, Heterocephalus glaber) are among the most hypoxia-tolerant mammals known. They can reduce their metabolic rate (>85%) under severe hypoxia, remain moderately active and recover with no obvious signs of damage. Hence, NMRs are an excellent model for studying mammalian hypoxia tolerance. The current study characterized the involvement of posttranslational modifications in regulating the Akt/mTOR pathway that regulates protein synthesis, and the responses of key ribosomal proteins in order to assess tissue-specific responses to 4 h exposure to 7% O2 (compared to controls at 21% O2). Results showed a tissue-specific regulation of the Akt/mTOR pathway via differential phosphorylation. Relative amounts of p-TSC(S939) in brain and of p-TSC(S939), p-Akt(473) and p-PTEN(S380) in liver increased under hypoxia, whereas levels of IGF1R(Y1135/1136) in liver decreased. In skeletal muscle, levels of p-Akt(S473) and p-PTEN(S380) decreased during hypoxia, whereas lungs showed an increase in p-mTOR(S2884) content but a decrease in p-RPS6(S235-236) under the same conditions. Analysis of the phosphorylation states of ribosomal proteins revealed increases in p-4E-BP1(T37/46) content in brain and lungs under hypoxia, as well as a rise in total 4E-BP1 protein level in liver. Phosphorylated eIF-4B(S422) content also increased in liver while levels of p-eIF-2α(S51), and eIF-4E(S209) decreased during hypoxia in liver. Overall, hypoxia altered the Akt/mTOR pathway, which correlated with a general decrease in activity of the ribosomal protein biosynthesis machinery in muscle, lung, and brain of NMRs. However, the increase in eIF-4B in liver suggests the potential promotion of cap-independent mRNA translation mechanism operating under hypoxic stress.

中文翻译：

---

差异蛋白磷酸化负责缺氧诱导裸mole鼠大鼠Akt / mTOR途径的调节。

裸mole鼠（NMR，Heterocephalus glaber）是已知的最耐缺氧的哺乳动物之一。在严重缺氧的情况下，它们可以降低代谢率（> 85％），保持中度活跃并可以恢复，没有明显的损害迹象。因此，NMR是研究哺乳动物低氧耐受性的绝佳模型。本研究的特点是翻译后修饰参与调节蛋白合成的Akt / mTOR途径的调控，以及关键核糖体蛋白的反应，以评估在7％O2下暴露4 h的组织特异性反应（与21岁对照组相比）。 ％O2）。结果显示通过差异磷酸化对Akt / mTOR途径的组织特异性调节。在缺氧条件下，脑中p-TSC（S939）和肝中p-TSC（S939），p-Akt（473）和p-PTEN（S380）的相对量增加，而肝脏中的IGF1R（Y1135 / 1136）水平下降。在缺氧条件下，骨骼肌中p-Akt（S473）和p-PTEN（S380）的水平降低，而在低氧条件下，肺部的p-mTOR（S2884）含量增加，而p-RPS6（S235-236）降低。相同的条件。核糖体蛋白的磷酸化状态分析表明，在缺氧条件下，脑和肺中p-4E-BP1（T37 / 46）含量增加，肝脏中总4E-BP1蛋白水平也升高。在肝脏缺氧期间，磷酸化的eIF-4B（S422）含量在肝脏中也增加，而p-eIF-2α（S51）和eIF-4E（S209）的水平降低。总体而言，缺氧改变了Akt / mTOR通路，这与NMR的肌肉，肺和脑中核糖体蛋白生物合成机制的活性普遍下降有关。然而，