Naked mole rats are a long‐lived animal model that age much like humans, but that can also withstand oxidative damage, cancer, neurodegenerative diseases, and severe hypoxic conditions, which is of particular interest to this study. The conditions of their underground burrows result in competition for oxygen consumption, yet despite this oxygen deprivation they emerge unscathed. To understand the mechanisms in place to facilitate neuronal preservation during hypoxia, we investigated the protein levels of well‐known cell‐stress factors. We found that under hypoxic conditions, nearly half of the proteins measured increased expression in brain, while only a few decreased. Under hypoxic conditions there appeared to be a HIF1α‐centered response, where HIF1α and its interactors carbonic anhydrase 9, CITED2, p21/CIP1, and NFκB1, among others, were upregulated. Concurrently, a hypoxia‐induced decrease of cytochrome c was consistent with decreased mitochondrial function and protection from apoptosis. The picture that emerges is one of neuroprotection, cell‐cycle arrest, and the promotion of antiapoptotic functions, all of which are consistent with conserving energy and maintaining neural integrity under low oxygen levels. These results suggest how this species may be poised to face hypoxia and contribute to its remarkable ability to deal with myriad of other damaging factors and sets the stage for future work on the neuroprotective facilitators we identified.

中文翻译：

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缺氧的裸mole鼠会激活神经保护蛋白。

裸mole鼠是一种寿命很长的动物模型，其年龄与人类相似，但也可以承受氧化损伤，癌症，神经退行性疾病和严重的低氧状况，这是本研究特别感兴趣的。他们地下洞穴的条件导致了对氧气消耗的竞争，尽管如此，氧气剥夺却使他们毫发无损。为了了解缺氧期间促进神经元保存的机制，我们研究了众所周知的细胞应激因子的蛋白质水平。我们发现，在缺氧条件下，近一半的蛋白质在大脑中表达增加，而只有少数蛋白质减少。在低氧条件下，似乎出现了以HIF1α为中心的反应，其中HIF1α及其相互作用物碳酸酐酶9，CITED2，p21 / CIP1和NFκB1等，被上调。同时，由缺氧引起的细胞色素减少c与线粒体功能降低和细胞凋亡保护相一致。出现的图像是神经保护，细胞周期停滞和抗凋亡功能的促进之一，所有这些都与在低氧水平下节省能量和维持神经完整性相一致。这些结果表明，该物种可能会面临缺氧的情况，并有助于其应对多种其他破坏性因素的出色能力，并为我们确定的神经保护促进剂的未来工作奠定了基础。