Development of cytosolic hypoxia and hypoxia-inducible factor stabilization are facilitated by aquaporin-1 expression
Development of cytosolic hypoxia and hypoxia-inducible factor stabilization are facilitated by aquaporin-1 expression
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DOI：
10.1074/jbc.m702639200
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发表时间：
2007-10-12
影响因子：
4.8
通讯作者：
Lopez-Barneo, Jose
中科院分区：
文献类型：
--
作者：
Echevarria, Miriam;Munoz-Cabello, Ana M.;Lopez-Barneo, Jose
O-2是有氧生活所必需的，经典的观点是它可以自由地穿过质膜扩散。然而，对脂双层O-2渗透性的测量表明，它比以前认为的要低得多，因此，表明膜O-2通道的存在。我们推测，水通道蛋白1（AQP-1）除了作为水通道的作用外，还可以作为O-2转运蛋白，因为这种跨膜蛋白似乎是CO2可渗透的，并且在具有快速O-2周转的细胞（红细胞和微血管内皮）中高度表达。在这里，我们表明，在哺乳动物细胞中过表达AQP-1和暴露于缺氧，胞质O-2的损失，以及O-2依赖性缺氧诱导转录因子和其靶基因的表达的稳定，加速。在含氧量正常的内皮细胞中，敲低AQP-1产生低氧诱导基因的诱导。此外，肺AQP-1在暴露于缺氧的动物中显著上调。这些数据表明，AQP-1具有O-2渗透性，因此可以促进O-2跨细胞膜扩散。
O-2 is essential for aerobic life, and the classic view is that it diffuses freely across the plasma membrane. However, measurements of O-2 permeability of lipid bilayers have indicated that it is much lower than previously thought, and therefore, the existence of membrane O-2 channels has been suggested. Wehypothesized that, besides its role as a water channel, aquaporin-1 (AQP-1) could also work as an O-2 transporter, because this transmembrane protein appears to be CO2-permeable and is highly expressed in cells with rapid O2 turnover (erythrocytes and microvessel endothelium). Here we show that in mammalian cells overexpressing AQP-1 and exposed to hypoxia, the loss of cytosolic O-2, as well as stabilization of the O-2-dependent hypoxia-inducible transcription factor and expression of its target genes, is accelerated. In normoxic endothelial cells, knocking down AQP-1 produces induction of hypoxia-inducible genes. Moreover, lung AQP-1 is markedly up-regulated in animals exposed to hypoxia. These data suggest that AQP-1 has O-2 permeability and thus could facilitate O-2 diffusion across the cell membrane.