Development of cytosolic hypoxia and hypoxia-inducible factor stabilization are facilitated by aquaporin-1 expression.
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. We hypothesized 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 CO(2)-permeable and is highly expressed in cells with rapid O(2) 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.
Echevarría
Miriam
M
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, 41013 Spain.
Muñoz-Cabello
Ana M
AM
Sánchez-Silva
Rocío
R
Toledo-Aral
Juan J
JJ
López-Barneo
José
J
D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis* / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D005786:Gene Expression Regulation; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D010539:Permeability; D051381:Rats; D015854:Up-Regulation
D051793:Hypoxia-Inducible Factor 1; D009593:Nitroimidazoles; D002245:Carbon Dioxide; D051398:Aquaporin 1; C033815:pimonidazole; D010100:Oxygen