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Physiol. Rev. 76: 839-885, 1996;
0031-9333/96 $15.00
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Physiological Reviews, Vol 76, 839-885, Copyright © 1996 by American Physiological Society

JOURNAL ARTICLE

Oxygen sensing and molecular adaptation to hypoxia

H. F. Bunn and R. O. Poyton
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Masachusetts, USA.

This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on reactive oxygen species. These heme-based sensors are generally two-domain proteins. Some are hemokinases, while others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1. In yeast and bacteria, regulatory operons coordinate expression of genes responsible for adaptive responses to hypoxia and hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with other identified transcription factors are required for the hypoxic induction of physiologically important genes.


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Regulation of oxygen sensing by ion channels
J Appl Physiol, March 1, 2004; 96(3): 1187 - 1195.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
N. C Chi and J. S Karliner
Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors
Cardiovasc Res, February 15, 2004; 61(3): 437 - 447.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
U. Roth, K. Curth, T. G. Unterman, and T. Kietzmann
The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway
J. Biol. Chem., January 23, 2004; 279(4): 2623 - 2631.
[Abstract] [Full Text] [PDF]

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 JEMHome page
J.-Y. Kim, H.-J. Ahn, J.-H. Ryu, K. Suk, and J.-H. Park
BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1{alpha}
J. Exp. Med., January 5, 2004; 199(1): 113 - 124.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
J. Prieto-Lloret, A. I. Caceres, A. Obeso, A. Rocher, R. Rigual, M. T. Agapito, R. Bustamante, J. Castaneda, M. T. Perez-Garcia, J. R. Lopez-Lopez, et al.
Ventilatory responses and carotid body function in adult rats perinatally exposed to hyperoxia
J. Physiol., January 1, 2004; 554(1): 126 - 144.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T. Hon, A. Dodd, R. Dirmeier, N. Gorman, P. R. Sinclair, L. Zhang, and R. O. Poyton
A Mechanism of Oxygen Sensing in Yeast: MULTIPLE OXYGEN-RESPONSIVE STEPS IN THE HEME BIOSYNTHETIC PATHWAY AFFECT Hap1 ACTIVITY
J. Biol. Chem., December 12, 2003; 278(50): 50771 - 50780.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Fantozzi, S. Zhang, O. Platoshyn, C. V. Remillard, R. T. Cowling, and J. X.-J. Yuan
Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1233 - L1245.
[Abstract] [Full Text] [PDF]

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 Toxicol SciHome page
J. M. Zodrow and R. L. Tanguay
2,3,7,8-Tetrachlorodibenzo-p-dioxin Inhibits Zebrafish Caudal Fin Regeneration
Toxicol. Sci., November 1, 2003; 76(1): 151 - 161.
[Abstract] [Full Text] [PDF]

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 BloodHome page
B. D. Schneider and E. A. Leibold
Effects of iron regulatory protein regulation on iron homeostasis during hypoxia
Blood, November 1, 2003; 102(9): 3404 - 3411.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
B. D. Eads and S. C. Hand
Mitochondrial mRNA stability and polyadenylation during anoxia-induced quiescence in the brine shrimp Artemia franciscana
J. Exp. Biol., October 15, 2003; 206(20): 3681 - 3692.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. O. Leonard, D. C. Cottell, C. Godson, H. R. Brady, and C. T. Taylor
The Role of HIF-1{alpha} in Transcriptional Regulation of the Proximal Tubular Epithelial Cell Response to Hypoxia
J. Biol. Chem., October 10, 2003; 278(41): 40296 - 40304.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
K. A. Webster
Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia
J. Exp. Biol., September 1, 2003; 206(17): 2911 - 2922.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
N. Masson and P. J. Ratcliffe
HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O2 levels
J. Cell Sci., August 1, 2003; 116(15): 3041 - 3049.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
Z. Dong, J. Z. Wang, F. Yu, and M. A. Venkatachalam
Apoptosis-Resistance of Hypoxic Cells: Multiple Factors Involved and a Role for IAP-2
Am. J. Pathol., August 1, 2003; 163(2): 663 - 671.
[Abstract] [Full Text] [PDF]

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 BloodHome page
M. J. Percy, M. F. McMullin, S. N. Jowitt, M. Potter, M. Treacy, W. H. Watson, and T. R. J. Lappin
Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry
Blood, August 1, 2003; 102(3): 1097 - 1099.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
S.-k. Park, A. M. Dadak, V. H. Haase, L. Fontana, A. J. Giaccia, and R. S. Johnson
Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1{alpha} (HIF-1{alpha}): Role of Cytoplasmic Trapping of HIF-2{alpha}
Mol. Cell. Biol., July 15, 2003; 23(14): 4959 - 4971.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
N. Linder, E. Martelin, R. Lapatto, and K. O. Raivio
Posttranslational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions
Am J Physiol Cell Physiol, July 1, 2003; 285(1): C48 - C55.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Del Toro, K. L. Levitsky, J. Lopez-Barneo, and M. D. Chiara
Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia
J. Biol. Chem., June 13, 2003; 278(25): 22316 - 22324.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
Y. Yasuda, Y. Fujita, T. Matsuo, S. Koinuma, S. Hara, A. Tazaki, M. Onozaki, M. Hashimoto, T. Musha, K. Ogawa, et al.
Erythropoietin regulates tumour growth of human malignancies
Carcinogenesis, June 1, 2003; 24(6): 1021 - 1029.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
V. T. Mihaylova, R. S. Bindra, J. Yuan, D. Campisi, L. Narayanan, R. Jensen, F. Giordano, R. S. Johnson, S. Rockwell, and P. M. Glazer
Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells
Mol. Cell. Biol., May 1, 2003; 23(9): 3265 - 3273.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
K. C. Boardman and M. A. Swartz
Interstitial Flow as a Guide for Lymphangiogenesis
Circ. Res., April 18, 2003; 92(7): 801 - 808.
[Abstract] [Full Text] [PDF]

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 Mol Cancer ResHome page
Y. Jiang, W. Zhang, K. Kondo, J. M. Klco, T. B. St. Martin, M. R. Dufault, S. L. Madden, W. G. Kaelin Jr, and M. Nacht
Gene Expression Profiling in a Renal Cell Carcinoma Cell Line: Dissecting VHL and Hypoxia-Dependent Pathways
Mol. Cancer Res., April 1, 2003; 1(6): 453 - 462.
[Abstract] [Full Text] [PDF]

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 J BiochemHome page
K. Nagao, S. Takenaka, R. Yamaji, H. Inui, and Y. Nakano
Nitric Oxide Synthase Induction, cGMP Elevation, and Biopterin Synthesis in Vascular Smooth Muscle Cells Stimulated with Interleukin-1{beta} in Hypoxia
J. Biochem., April 1, 2003; 133(4): 501 - 505.
[Abstract] [Full Text] [PDF]

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 Plant Physiol.Home page
J. T. van Dongen, U. Schurr, M. Pfister, and P. Geigenberger
Phloem Metabolism and Function Have to Cope with Low Internal Oxygen
Plant Physiology, April 1, 2003; 131(4): 1529 - 1543.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
Y. Sun, K. Jin, A. Peel, X. O. Mao, L. Xie, and D. A. Greenberg
Neuroglobin protects the brain from experimental stroke invivo
PNAS, March 18, 2003; 100(6): 3497 - 3500.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
K. M. Comerford, M. O. Leonard, J. Karhausen, R. Carey, S. P. Colgan, and C. T. Taylor
Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia
PNAS, February 4, 2003; 100(3): 986 - 991.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
J. Zhou, J. Fandrey, J. Schumann, G. Tiegs, and B. Brune
NO and TNF-alpha released from activated macrophages stabilize HIF-1alpha in resting tubular LLC-PK1 cells
Am J Physiol Cell Physiol, February 1, 2003; 284(2): C439 - C446.
[Abstract] [Full Text] [PDF]


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