Hypoxia activates IKK-NF-κB and the immune response in Drosophila melanogaster.
Hypoxia activates IKK-NF-κB and the immune response in Drosophila melanogaster.
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DOI：
10.1042/bsr20140095
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发表时间：
2014-07-29
影响因子：
4
通讯作者：
Rocha S
中科院分区：
文献类型：
--
作者：
Bandarra D;Biddlestone J;Mudie S;Muller HA;Rocha S
缺氧或低氧可用性是多细胞生物的重要生理和病理刺激。在分子水平上，缺氧激活了一个转录程序，旨在恢复氧稳态和细胞存活。在哺乳动物细胞中，缺氧不仅激活HIF（缺氧诱导因子）家族，而且还激活其他转录因子，如NF-κB（核因子κB）。在这里，我们表明，缺氧激活IKK-NF-κB [IκB（核因子κB的抑制剂）-NF-κB]途径和免疫反应的果蝇。我们发现NF-κB活化是机体在缺氧条件下生存所必需的。最后，我们确定了肿瘤抑制因子Cyld的作用，作为一个负调节NF-κB在果蝇缺氧反应。结果表明，低氧激活IKK-NF-κB通路和免疫应答是一种重要的、进化上保守的应答。在这里，我们证明了低氧激活转录因子，NF-κB和果蝇的免疫反应。我们发现低氧后NF-κB反应的失调导致这些动物的存活率降低。
Hypoxia, or low oxygen availability, is an important physiological and pathological stimulus for multicellular organisms. Molecularly, hypoxia activates a transcriptional programme directed at restoration of oxygen homoeostasis and cellular survival. In mammalian cells, hypoxia not only activates the HIF (hypoxia-inducible factor) family, but also additional transcription factors such as NF-κB (nuclear factor κB). Here we show that hypoxia activates the IKK–NF-κB [IκB (inhibitor of nuclear factor κB)–NF-κB] pathway and the immune response in Drosophila melanogaster. We show that NF-κB activation is required for organism survival in hypoxia. Finally, we identify a role for the tumour suppressor Cyld, as a negative regulator of NF-κB in response to hypoxia in Drosophila. The results indicate that hypoxia activation of the IKK–NF-κB pathway and the immune response is an important and evolutionary conserved response. Here we demonstrate that low oxygen activates the transcription factor, NF-κB and the immune response in Drosophila. We show that deregulation of the NF-κB response following low oxygen, results in decreased survival of these animals.