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Science 302 (5652): 1975-1978

Copyright © 2003 by the American Association for the Advancement of Science

Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1{alpha}

Thilo Hagen,1 Cormac T. Taylor,2 Francis Lam,1 Salvador Moncada1*

Abstract: Cells exposed to low oxygen concentrations respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1{alpha}, a transcription factor that upregulates genes such as those involved in glycolysis and angiogenesis. Nitric oxide and other inhibitors of mitochondrial respiration prevent the stabilization of HIF1{alpha} during hypoxia. In studies of cultured cells, we show that this effect is a result of an increase in prolyl hydroxylase–dependent degradation of HIF1{alpha}. With the use of Renilla luciferase to detect intracellular oxygen concentrations, we also demonstrate that, upon inhibition of mitochondrial respiration in hypoxia, oxygen is redistributed toward nonrespiratory oxygen-dependent targets such as prolyl hydroxylases so that they do not register hypoxia. Thus, the signaling consequences of hypoxia may be profoundly modified by nitric oxide.

1 Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
2 Conway Institute for Biomedical and Biochemical Research, University College Dublin 4, Belfield, Dublin, Ireland.

* To whom correspondence should be addressed. E-mail: s.moncada{at}

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Cell Sci. 126, 1454-1463
   Abstract »    Full Text »    PDF »
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N. R. Prabhakar and G. L. Semenza (2012)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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I. B. Barsoum, T. K. Hamilton, X. Li, T. Cotechini, E. A. Miles, D. R. Siemens, and C. H. Graham (2011)
Cancer Res. 71, 7433-7441
   Abstract »    Full Text »    PDF »
Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia.
A. Vanhatalo, J. Fulford, S. J. Bailey, J. R. Blackwell, P. G. Winyard, and A. M. Jones (2011)
J. Physiol. 589, 5517-5528
   Abstract »    Full Text »    PDF »
Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia.
A. K. Y. Tsui, P. A. Marsden, C. D. Mazer, S. L. Adamson, R. M. Henkelman, J. J. D. Ho, D. F. Wilson, S. P. Heximer, K. A. Connelly, S.-S. Bolz, et al. (2011)
PNAS 108, 17544-17549
   Abstract »    Full Text »    PDF »
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I. Serganova, A. Rizwan, X. Ni, S. B. Thakur, J. Vider, J. Russell, R. Blasberg, and J. A. Koutcher (2011)
Clin. Cancer Res. 17, 6250-6261
   Abstract »    Full Text »    PDF »
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J. Heidler, N. Al-Furoukh, C. Kukat, I. Salwig, M.-E. Ingelmann, P. Seibel, M. Kruger, J. Holtz, I. Wittig, T. Braun, et al. (2011)
J. Biol. Chem. 286, 32086-32093
   Abstract »    Full Text »    PDF »
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K. J. Smith (2011)
Brain 134, 1877-1881
   Full Text »    PDF »
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Y. Sato, H. Endo, H. Okuyama, T. Takeda, H. Iwahashi, A. Imagawa, K. Yamagata, I. Shimomura, and M. Inoue (2011)
J. Biol. Chem. 286, 12524-12532
   Abstract »    Full Text »    PDF »
NRF2 Blockade Suppresses Colon Tumor Angiogenesis by Inhibiting Hypoxia-Induced Activation of HIF-1{alpha}.
T.-H. Kim, E.-g. Hur, S.-J. Kang, J.-A. Kim, D. Thapa, Y. M. Lee, S. K. Ku, Y. Jung, and M.-K. Kwak (2011)
Cancer Res. 71, 2260-2275
   Abstract »    Full Text »    PDF »
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Y. Takiyama, T. Harumi, J. Watanabe, Y. Fujita, J. Honjo, N. Shimizu, Y. Makino, and M. Haneda (2011)
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   Abstract »    Full Text »    PDF »
Imaging of oxygen gradients in monolayer cultured cells using green fluorescent protein.
E. Takahashi and M. Sato (2010)
Am J Physiol Cell Physiol 299, C1318-C1323
   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 285, 31277-31284
   Abstract »    Full Text »    PDF »
Ancient Atmospheres and the Evolution of Oxygen Sensing Via the Hypoxia-Inducible Factor in Metazoans.
C. T. Taylor and J. C. McElwain (2010)
Physiology 25, 272-279
   Abstract »    Full Text »    PDF »
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K. A. Borley, J. M. Beers, and B. D. Sidell (2010)
J. Exp. Biol. 213, 2865-2872
   Abstract »    Full Text »    PDF »
{beta}2- but not {beta}1-adrenoceptor activation modulates intracellular oxygen availability.
J. Li, B. Yan, Z. Huo, Y. Liu, J. Xu, Y. Sun, Y. Liu, D. Liang, L. Peng, Y. Zhang, et al. (2010)
J. Physiol. 588, 2987-2998
   Abstract »    Full Text »    PDF »
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F. J. Giordano (2010)
Arterioscler Thromb Vasc Biol 30, 641-642
   Full Text »    PDF »
Nitric Oxide, Cytochrome C Oxidase, and the Cellular Response to Hypoxia.
C. T. Taylor and S. Moncada (2010)
Arterioscler Thromb Vasc Biol 30, 643-647
   Abstract »    Full Text »    PDF »
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T. Tanaka, T. Wakamatsu, H. Daijo, S. Oda, S. Kai, T. Adachi, S. Kizaka-Kondoh, K. Fukuda, and K. Hirota (2010)
Am J Physiol Regulatory Integrative Comp Physiol 298, R661-R671
   Abstract »    Full Text »    PDF »
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A. V. Ivanina, S. Eilers, I. O. Kurochkin, J. S. Chung, S. Techa, H. Piontkivska, E. P. Sokolov, and I. M. Sokolova (2010)
J. Exp. Biol. 213, 433-444
   Abstract »    Full Text »    PDF »
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D. Wang, D. Malo, and S. Hekimi (2010)
J. Immunol. 184, 582-590
   Abstract »    Full Text »    PDF »
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D. Ortiz-Masia, C. Hernandez, E. Quintana, M. Velazquez, S. Cebrian, A. Riano, S. Calatayud, J. V. Esplugues, and M. D. Barrachina (2010)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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A. Galkin, A. Y. Abramov, N. Frakich, M. R. Duchen, and S. Moncada (2009)
J. Biol. Chem. 284, 36055-36061
   Abstract »    Full Text »    PDF »
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J Appl Physiol 107, 1144-1155
   Abstract »    Full Text »    PDF »
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L. Gunaratnam and J. V. Bonventre (2009)
J. Am. Soc. Nephrol. 20, 1877-1887
   Abstract »    Full Text »    PDF »
Hypoxia-inducible Factor Prolyl-4-hydroxylase PHD2 Protein Abundance Depends on Integral Membrane Anchoring of FKBP38.
S. Barth, F. Edlich, U. Berchner-Pfannschmidt, S. Gneuss, G. Jahreis, P. A. Hasgall, J. Fandrey, R. H. Wenger, and G. Camenisch (2009)
J. Biol. Chem. 284, 23046-23058
   Abstract »    Full Text »    PDF »
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M. Schleicher, J. Yu, T. Murata, B. Derakhshan, D. Atochin, L. Qian, S. Kashiwagi, A. Di Lorenzo, K. D. Harrison, P. L. Huang, et al. (2009)
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   Abstract »    Full Text »    PDF »
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D. A. Tennant, R. V. Duran, H. Boulahbel, and E. Gottlieb (2009)
Carcinogenesis 30, 1269-1280
   Abstract »    Full Text »    PDF »
A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury.
T. A. Prime, F. H. Blaikie, C. Evans, S. M. Nadtochiy, A. M. James, C. C. Dahm, D. A. Vitturi, R. P. Patel, C. R. Hiley, I. Abakumova, et al. (2009)
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   Abstract »    Full Text »    PDF »
Reactive Oxygen Species-independent Oxidation of Thioredoxin in Hypoxia: INACTIVATION OF RIBONUCLEOTIDE REDUCTASE AND REDOX-MEDIATED CHECKPOINT CONTROL.
H. Muniyappa, S. Song, C. K. Mathews, and K. C. Das (2009)
J. Biol. Chem. 284, 17069-17081
   Abstract »    Full Text »    PDF »
Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments.
T. Zaobornyj, L. B. Valdez, D. E. Iglesias, M. Gasco, G. F. Gonzales, and A. Boveris (2009)
Am J Physiol Heart Circ Physiol 296, H1741-H1747
   Abstract »    Full Text »    PDF »
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M. T. Gladwin and S. Shiva (2009)
Circ. Res. 104, 1136-1138
   Full Text »    PDF »
Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide.
V. M. Victor, C. Nunez, P. D'Ocon, C. T. Taylor, J. V. Esplugues, and S. Moncada (2009)
Circ. Res. 104, 1178-1183
   Abstract »    Full Text »    PDF »
Nitric oxide increases myocardial efficiency in the hypoxia-tolerant turtle Trachemys scripta.
M. Misfeldt, A. Fago, and H. Gesser (2009)
J. Exp. Biol. 212, 954-960
   Abstract »    Full Text »    PDF »
eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues.
J.-L. Balligand, O. Feron, and C. Dessy (2009)
Physiol Rev 89, 481-534
   Abstract »    Full Text »    PDF »
Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling.
L. Gao and G. E. Mann (2009)
Cardiovasc Res 82, 9-20
   Abstract »    Full Text »    PDF »
PGC-1{alpha} is coupled to HIF-1{alpha}-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells.
K. A. O'Hagan, S. Cocchiglia, A. V. Zhdanov, M. M. Tambuwala, E. P. Cummins, M. Monfared, T. A. Agbor, J. F. Garvey, D. B. Papkovsky, C. T. Taylor, et al. (2009)
PNAS 106, 2188-2193
   Abstract »    Full Text »    PDF »
The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF.
S. Beyer, M. M. Kristensen, K. S. Jensen, J. V. Johansen, and P. Staller (2008)
J. Biol. Chem. 283, 36542-36552
   Abstract »    Full Text »    PDF »
Can O2 Dysregulation Induce Premature Aging?.
R. M. Douglas and G. G. Haddad (2008)
Physiology 23, 333-349
   Abstract »    Full Text »    PDF »
Activation of Hsp90-eNOS and increased NO generation attenuate respiration of hypoxia-treated endothelial cells.
T. Presley, K. Vedam, M. Velayutham, J. L. Zweier, and G. Ilangovan (2008)
Am J Physiol Cell Physiol 295, C1281-C1291
   Abstract »    Full Text »    PDF »
Oxygen- and NssR-dependent Globin Expression and Enhanced Iron Acquisition in the Response of Campylobacter to Nitrosative Stress.
C. E. Monk, B. M. Pearson, F. Mulholland, H. K. Smith, and R. K. Poole (2008)
J. Biol. Chem. 283, 28413-28425
   Abstract »    Full Text »    PDF »
The functional nitrite reductase activity of the heme-globins.
M. T. Gladwin and D. B. Kim-Shapiro (2008)
Blood 112, 2636-2647
   Abstract »    Full Text »    PDF »
Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1{alpha} Differentially in Cancer and Ischemia.
A. A. Qutub and A. S. Popel (2008)
Mol. Cell. Biol. 28, 5106-5119
   Abstract »    Full Text »    PDF »
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C. N. Hall and D. Attwell (2008)
J. Physiol. 586, 3597-3615
   Abstract »    Full Text »    PDF »
Hypoxia-Inducible Factor-1 Is Central to Cardioprotection: A New Paradigm for Ischemic Preconditioning.
T. Eckle, D. Kohler, R. Lehmann, K. C. El Kasmi, and H. K. Eltzschig (2008)
Circulation 118, 166-175
   Abstract »    Full Text »    PDF »
Nitric Oxide Donor, ({+/-})-S-Nitroso-N-acetylpenicillamine, Stabilizes Transactive Hypoxia-Inducible Factor-1{alpha} by Inhibiting von Hippel-Lindau Recruitment and Asparagine Hydroxylation.
Y.-K. Park, D.-R. Ahn, M. Oh, T. Lee, E. G. Yang, M. Son, and H. Park (2008)
Mol. Pharmacol. 74, 236-245
   Abstract »    Full Text »    PDF »
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C. T. Taylor (2008)
Am J Physiol Cell Physiol 294, C1300-C1302
   Full Text »    PDF »
Induction of HIF-2{alpha} is dependent on mitochondrial O2 consumption in an O2-sensitive adrenomedullary chromaffin cell line.
S. T. Brown and C. A. Nurse (2008)
Am J Physiol Cell Physiol 294, C1305-C1312
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of SDHa Flavoprotein by Nuclear Respiratory Factor-1 Prevents Pseudo-hypoxia in Aerobic Cardiac Cells.
C. A. Piantadosi and H. B. Suliman (2008)
J. Biol. Chem. 283, 10967-10977
   Abstract »    Full Text »    PDF »
PHDs overactivation during chronic hypoxia "desensitizes" HIF{alpha} and protects cells from necrosis.
A. Ginouves, K. Ilc, N. Macias, J. Pouyssegur, and E. Berra (2008)
PNAS 105, 4745-4750
   Abstract »    Full Text »    PDF »
Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology: Focus on Angiogenesis.
J. Dulak, J. Deshane, A. Jozkowicz, and A. Agarwal (2008)
Circulation 117, 231-241
   Abstract »    Full Text »    PDF »
A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation.
X. Lin, C. A. David, J. B. Donnelly, M. Michaelides, N. S. Chandel, X. Huang, U. Warrior, F. Weinberg, K. V. Tormos, S. W. Fesik, et al. (2008)
PNAS 105, 174-179
   Abstract »    Full Text »    PDF »
Detection of Reactive Oxygen Species via Endogenous Oxidative Pentose Phosphate Cycle Activity in Response to Oxygen Concentration: IMPLICATIONS FOR THE MECHANISM OF HIF-1{alpha} STABILIZATION UNDER MODERATE HYPOXIA.
S. W. Tuttle, A. Maity, P. R. Oprysko, A. V. Kachur, I. S. Ayene, J. E. Biaglow, and C. J. Koch (2007)
J. Biol. Chem. 282, 36790-36796
   Abstract »    Full Text »    PDF »
Nitric Oxide and Mitochondrial Signaling: From Physiology to Pathophysiology.
J. D. Erusalimsky and S. Moncada (2007)
Arterioscler Thromb Vasc Biol 27, 2524-2531
   Abstract »    Full Text »    PDF »
Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: A possible explanation for hypoxic vasodilation.
M. Palacios-Callender, V. Hollis, M. Mitchison, N. Frakich, D. Unitt, and S. Moncada (2007)
PNAS 104, 18508-18513
   Abstract »    Full Text »    PDF »
Development of Cytosolic Hypoxia and Hypoxia-inducible Factor Stabilization Are Facilitated by Aquaporin-1 Expression.
M. Echevarria, A. M. Munoz-Cabello, R. Sanchez-Silva, J. J. Toledo-Aral, and J. Lopez-Barneo (2007)
J. Biol. Chem. 282, 30207-30215
   Abstract »    Full Text »    PDF »
Rat carotid body chemosensory discharge and glomus cell HIF-1{alpha} expression in vitro: regulation by a common oxygen sensor.
A. Roy, S. M. Baby, D. F. Wilson, and S. Lahiri (2007)
Am J Physiol Regulatory Integrative Comp Physiol 293, R829-R836
   Abstract »    Full Text »    PDF »
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production.
E. L. Bell, T. A. Klimova, J. Eisenbart, C. T. Moraes, M. P. Murphy, G.R. S. Budinger, and N. S. Chandel (2007)
J. Cell Biol. 177, 1029-1036
   Abstract »    Full Text »    PDF »
Nitric oxide and superoxide: Interference with hypoxic signaling.
B. Brune and J. Zhou (2007)
Cardiovasc Res 75, 275-282
   Abstract »    Full Text »    PDF »
Substrate-mediated Regulation of Cullin Neddylation.
E.-H. Chew and T. Hagen (2007)
J. Biol. Chem. 282, 17032-17040
   Abstract »    Full Text »    PDF »
Hypoxia-inducible Factor-1{alpha}, a Key Factor in the Keratinocyte Response to UVB Exposure.
H. R. Rezvani, S. Dedieu, S. North, F. Belloc, R. Rossignol, T. Letellier, H. de Verneuil, A. Taieb, and F. Mazurier (2007)
J. Biol. Chem. 282, 16413-16422
   Abstract »    Full Text »    PDF »
Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology.
C. E. Cooper and C. Giulivi (2007)
Am J Physiol Cell Physiol 292, C1993-C2003
   Abstract »    Full Text »    PDF »
Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy.
R. A. Cairns, I. Papandreou, P. D. Sutphin, and N. C. Denko (2007)
PNAS 104, 9445-9450
   Abstract »    Full Text »    PDF »
Sensing intracellular oxygen using near-infrared phosphorescent probes and live-cell fluorescence imaging.
T. C. O'Riordan, K. Fitzgerald, G. V. Ponomarev, J. Mackrill, J. Hynes, C. Taylor, and D. B. Papkovsky (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R1613-R1620
   Abstract »    Full Text »    PDF »
Hypoxia-inducible factor 1{alpha} stabilization by carbon monoxide results in cytoprotective preconditioning.
B. Y. Chin, G. Jiang, B. Wegiel, H. J. Wang, T. MacDonald, X. C. Zhang, D. Gallo, E. Cszimadia, F. H. Bach, P. J. Lee, et al. (2007)
PNAS 104, 5109-5114
   Abstract »    Full Text »    PDF »
Deoxymyoglobin Is a Nitrite Reductase That Generates Nitric Oxide and Regulates Mitochondrial Respiration.
S. Shiva, Z. Huang, R. Grubina, J. Sun, L. A. Ringwood, P. H. MacArthur, X. Xu, E. Murphy, V. M. Darley-Usmar, and M. T. Gladwin (2007)
Circ. Res. 100, 654-661
   Abstract »    Full Text »    PDF »
Structural and Mechanistic Studies on the Inhibition of the Hypoxia-inducible Transcription Factor Hydroxylases by Tricarboxylic Acid Cycle Intermediates.
K. S. Hewitson, B. M. R. Lienard, M. A. McDonough, I. J. Clifton, D. Butler, A. S. Soares, N. J. Oldham, L. A. McNeill, and C. J. Schofield (2007)
J. Biol. Chem. 282, 3293-3301
   Abstract »    Full Text »    PDF »
Multiple Factors Affecting Cellular Redox Status and Energy Metabolism Modulate Hypoxia-Inducible Factor Prolyl Hydroxylase Activity In Vivo and In Vitro.
Y. Pan, K. D. Mansfield, C. C. Bertozzi, V. Rudenko, D. A. Chan, A. J. Giaccia, and M. C. Simon (2007)
Mol. Cell. Biol. 27, 912-925
   Abstract »    Full Text »    PDF »
Nitric Oxide Modulates Oxygen Sensing by Hypoxia-inducible Factor 1-dependent Induction of Prolyl Hydroxylase 2.
U. Berchner-Pfannschmidt, H. Yamac, B. Trinidad, and J. Fandrey (2007)
J. Biol. Chem. 282, 1788-1796
   Abstract »    Full Text »    PDF »
Amplification of Tumor Hypoxic Responses by Macrophage Migration Inhibitory Factor-Dependent Hypoxia-Inducible Factor Stabilization.
M. Winner, A. C. Koong, B. E. Rendon, W. Zundel, and R. A. Mitchell (2007)
Cancer Res. 67, 186-193
   Abstract »    Full Text »    PDF »
Increased expression of HIF-1{alpha}, nNOS, and VEGF in the cerebral cortex of anemic rats.
A. T. McLaren, P. A. Marsden, C. D. Mazer, A. J. Baker, D. J. Stewart, A. K. Y. Tsui, X. Li, Y. Yucel, M. Robb, S. R. Boyd, et al. (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R403-R414
   Abstract »    Full Text »    PDF »
Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology.
C. Giulivi, K. Kato, and C. E. Cooper (2006)
Am J Physiol Cell Physiol 291, C1225-C1231
   Abstract »    Full Text »    PDF »
Prolyl hydroxylase-1 negatively regulates I{kappa}B kinase-beta, giving insight into hypoxia-induced NF{kappa}B activity.
E. P. Cummins, E. Berra, K. M. Comerford, A. Ginouves, K. T. Fitzgerald, F. Seeballuck, C. Godson, J. E. Nielsen, P. Moynagh, J. Pouyssegur, et al. (2006)
PNAS 103, 18154-18159
   Abstract »    Full Text »    PDF »
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H. Yasuda, K. Nakayama, M. Watanabe, S. Suzuki, H. Fuji, S. Okinaga, A. Kanda, K. Zayasu, T. Sasaki, M. Asada, et al. (2006)
Clin. Cancer Res. 12, 6748-6757
   Abstract »    Full Text »    PDF »
Hypoxia-Inducible Factor-1 (HIF-1).
Q. Ke and M. Costa (2006)
Mol. Pharmacol. 70, 1469-1480
   Abstract »    Full Text »    PDF »
Regulating cellular oxygen sensing by hydroxylation.
J. Fandrey, T. A. Gorr, and M. Gassmann (2006)
Cardiovasc Res 71, 642-651
   Abstract »    Full Text »    PDF »
Hypoxia-inducible factors in the kidney.
V. H. Haase (2006)
Am J Physiol Renal Physiol 291, F271-F281
   Abstract »    Full Text »    PDF »
Nitric oxide and mitochondrial biogenesis.
E. Nisoli and M. O. Carruba (2006)
J. Cell Sci. 119, 2855-2862
   Abstract »    Full Text »    PDF »
The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases.
T. Acker, J. Fandrey, and H. Acker (2006)
Cardiovasc Res 71, 195-207
   Abstract »    Full Text »    PDF »
Inhibition of cellular respiration by endogenously produced carbon monoxide.
G. D'Amico, F. Lam, T. Hagen, and S. Moncada (2006)
J. Cell Sci. 119, 2291-2298
   Abstract »    Full Text »    PDF »
Adventures in vascular biology: a tale of two mediators.
S. Moncada (2006)
Phil Trans R Soc B 361, 735-759
   Abstract »    Full Text »    PDF »
Persistent S-Nitrosation of Complex I and Other Mitochondrial Membrane Proteins by S-Nitrosothiols but Not Nitric Oxide or Peroxynitrite: IMPLICATIONS FOR THE INTERACTION OF NITRIC OXIDE WITH MITOCHONDRIA.
C. C. Dahm, K. Moore, and M. P. Murphy (2006)
J. Biol. Chem. 281, 10056-10065
   Abstract »    Full Text »    PDF »
Mitochondria as signaling organelles in the vascular endothelium.
M. Quintero, S. L. Colombo, A. Godfrey, and S. Moncada (2006)
PNAS 103, 5379-5384
   Abstract »    Full Text »    PDF »
Calpain Mediates a von Hippel-Lindau Protein-independent Destruction of Hypoxia-inducible Factor-1{alpha}.
J. Zhou, R. Kohl, B. Herr, R. Frank, and B. Brune (2006)
Mol. Biol. Cell 17, 1549-1558
   Abstract »    Full Text »    PDF »
Randomized Phase II Trial Comparing Nitroglycerin Plus Vinorelbine and Cisplatin With Vinorelbine and Cisplatin Alone in Previously Untreated Stage IIIB/IV Non-Small-Cell Lung Cancer.
H. Yasuda, M. Yamaya, K. Nakayama, T. Sasaki, S. Ebihara, A. Kanda, M. Asada, D. Inoue, T. Suzuki, T. Okazaki, et al. (2006)
J. Clin. Oncol. 24, 688-694
   Abstract »    Full Text »    PDF »
Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase.
M. G. Mason, P. Nicholls, M. T. Wilson, and C. E. Cooper (2006)
PNAS 103, 708-713
   Abstract »    Full Text »    PDF »
Nitric Oxide Is a Factor in the Stabilization of Hypoxia-Inducible Factor-1{alpha} in Cancer: Role of Free Radical Formation.
M. Quintero, P. A. Brennan, G. J. Thomas, and S. Moncada (2006)
Cancer Res. 66, 770-774
   Abstract »    Full Text »    PDF »
The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling.
E. Berra, A. Ginouves, and J. Pouyssegur (2006)
EMBO Rep. 7, 41-45
   Abstract »    Full Text »    PDF »
The oxygen sensing signal cascade under the influence of reactive oxygen species.
H. Acker (2005)
Phil Trans R Soc B 360, 2201-2210
   Abstract »    Full Text »    PDF »
Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO.
C. Nunez, V. M. Victor, R. Tur, A. Alvarez-Barrientos, S. Moncada, J. V. Esplugues, and P. D'Ocon (2005)
Circ. Res. 97, 1063-1069
   Abstract »    Full Text »    PDF »
Selective Activation of Inflammatory Pathways by Intermittent Hypoxia in Obstructive Sleep Apnea Syndrome.
S. Ryan, C. T. Taylor, and W. T. McNicholas (2005)
Circulation 112, 2660-2667
   Abstract »    Full Text »    PDF »
Integration of Oxygen Signaling at the Consensus HRE.
R. H. Wenger, D. P. Stiehl, and G. Camenisch (2005)
Sci. STKE 2005, re12
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