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Previous Article | Table of Contents | Next Article 
Desferrioxamine induces erythropoietin gene expression and hypoxia-
inducible factor 1 DNA-binding activity: implications for models of hypoxia
signal transduction
GL Wang and GL Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine,
Baltimore, MD.
Erythropoietin (EPO) gene transcription is activated in kidney cells in
vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia-
inducible factor 1 (HIF-1) is a nuclear factor that binds to the
hypoxia-inducible enhancer of the EPO gene at a site that is required for
transcriptional activation. HIF-1 DNA-binding activity is induced by
hypoxia or cobalt chloride treatment of Hep3B cells. We report that
treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity
and EPO RNA expression with kinetics similar to the induction of HIF-1 by
hypoxia or cobalt chloride. Induction by each of these stimuli was
inhibited by cycloheximide, indicating a requirement for de novo protein
synthesis. DFX appears to induce HIF-1 by chelating iron as induction was
inhibited by coadministration of ferrous ammonium sulfate. DFX
administration to mice transiently increased EPO RNA levels in the kidney.
As previously shown for hypoxia and cobalt treatment, DFX also induced
HIF-1 activity in non-EPO-producing cells, suggesting the existence of a
common hypoxia signal-transduction pathway leading to HIF-1 induction in
different cell types.
Volume 82,
Issue 12,
pp. 3610-3615,
12/15/1993
Copyright © 1993 by The American Society of Hematology

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M. J. Grimshaw, S. Naylor, and F. R. Balkwill
Endothelin-2 Is a Hypoxia-induced Autocrine Survival Factor for Breast Tumor Cells
Mol. Cancer Ther.,
December 1, 2002;
1(14):
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[Abstract]
[Full Text]
[PDF]
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L.-M. Postovit, M. A. Adams, G. E. Lash, J. P. Heaton, and C. H. Graham
Oxygen-mediated Regulation of Tumor Cell Invasiveness. INVOLVEMENT OF A NITRIC OXIDE SIGNALING PATHWAY
J. Biol. Chem.,
September 13, 2002;
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[Abstract]
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[PDF]
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G. Ambrosini, A. K. Nath, M. R. Sierra-Honigmann, and J. Flores-Riveros
Transcriptional Activation of the Human Leptin Gene in Response to Hypoxia. INVOLVEMENT OF HYPOXIA-INDUCIBLE FACTOR 1
J. Biol. Chem.,
September 6, 2002;
277(37):
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[Abstract]
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K. A. Seta, Z. Spicer, Y. Yuan, G. Lu, and D. E. Millhorn
Responding to Hypoxia: Lessons From a Model Cell Line
Sci. Signal.,
August 20, 2002;
2002(146):
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[Abstract]
[Full Text]
[PDF]
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C. Treins, S. Giorgetti-Peraldi, J. Murdaca, G. L. Semenza, and E. Van Obberghen
Insulin Stimulates Hypoxia-inducible Factor 1 through a Phosphatidylinositol 3-Kinase/Target of Rapamycin-dependent Signaling Pathway
J. Biol. Chem.,
July 26, 2002;
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[Abstract]
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G. M. Balanos, K. L. Dorrington, and P. A. Robbins
Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1
J Appl Physiol,
June 1, 2002;
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[Abstract]
[Full Text]
[PDF]
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M. Alvarez-Tejado, A. Alfranca, J. Aragones, A. Vara, M. O. Landazuri, and L. del Peso
Lack of Evidence for the Involvement of the Phosphoinositide 3-Kinase/Akt Pathway in the Activation of Hypoxia-inducible Factors by Low Oxygen Tension
J. Biol. Chem.,
April 12, 2002;
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[Abstract]
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A. Eggert, M. A. Grotzer, N. Ikegaki, X.-g. Liu, A. E. Evans, and G. M. Brodeur
Expression of the Neurotrophin Receptor TrkA Down-Regulates Expression and Function of Angiogenic Stimulators in SH-SY5Y Neuroblastoma Cells
Cancer Res.,
March 1, 2002;
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[Abstract]
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Z.-Z. Yang and A.-P. Zou
Transcriptional regulation of heme oxygenases by HIF-1alpha in renal medullary interstitial cells
Am J Physiol Renal Physiol,
November 1, 2001;
281(5):
F900 - F908.
[Abstract]
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A.-P. ZOU, Z.-Z. YANG, P.-L. LI, and A. W. COWLEY JR.
Oxygen-dependent expression of hypoxia-inducible factor-1{alpha} in renal medullary cells of rats
Physiol Genomics,
August 28, 2001;
6(3):
159 - 168.
[Abstract]
[Full Text]
[PDF]
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D. A. Davis, A. S. Rinderknecht, J. P. Zoeteweij, Y. Aoki, E. L. Read-Connole, G. Tosato, A. Blauvelt, and R. Yarchoan
Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus
Blood,
May 15, 2001;
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3244 - 3250.
[Abstract]
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L. Carta, S. Pastorino, G. Melillo, M. C. Bosco, S. Massazza, and L. Varesio
Engineering of Macrophages to Produce IFN-{{gamma}} in Response to Hypoxia
J. Immunol.,
May 1, 2001;
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[Abstract]
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A. Rajakumar, K. A. Whitelock, L. A. Weissfeld, A. R. Daftary, N. Markovic, and K. P. Conrad
Selective Overexpression of the Hypoxia-Inducible Transcription Factor, HIF-2{{alpha}}, in Placentas from Women with Preeclampsia
Biol Reprod,
February 1, 2001;
64(2):
499 - 506.
[Abstract]
[Full Text]
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C. C. Wykoff, N. J. P. Beasley, P. H. Watson, K. J. Turner, J. Pastorek, A. Sibtain, G. D. Wilson, H. Turley, K. L. Talks, P. H. Maxwell, et al.
Hypoxia-inducible Expression of Tumor-associated Carbonic Anhydrases
Cancer Res.,
December 1, 2000;
60(24):
7075 - 7083.
[Abstract]
[Full Text]
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K. A. Vincent, K.-G. Shyu, Y. Luo, M. Magner, R. A. Tio, C. Jiang, M. A. Goldberg, G. Y. Akita, R. J. Gregory, and J. M. Isner
Angiogenesis Is Induced in a Rabbit Model of Hindlimb Ischemia by Naked DNA Encoding an HIF-1{alpha}/VP16 Hybrid Transcription Factor
Circulation,
October 31, 2000;
102(18):
2255 - 2261.
[Abstract]
[Full Text]
[PDF]
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G. L. Semenza
HIF-1 and human disease: one highly involved factor
Genes & Dev.,
August 15, 2000;
14(16):
1983 - 1991.
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R. M. Wanner, P. Spielmann, D. M. Stroka, G. Camenisch, I. Camenisch, A. Scheid, D. R. Houck, C. Bauer, M. Gassmann, and R. H. Wenger
Epolones induce erythropoietin expression via hypoxia-inducible factor-1alpha activation
Blood,
August 15, 2000;
96(4):
1558 - 1565.
[Abstract]
[Full Text]
[PDF]
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X. Ren, K. L. Dorrington, P. H. Maxwell, and P. A. Robbins
Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans
J Appl Physiol,
August 1, 2000;
89(2):
680 - 686.
[Abstract]
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R. K. Bruick
Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia
PNAS,
August 1, 2000;
97(16):
9082 - 9087.
[Abstract]
[Full Text]
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A. Rajakumar and K. P. Conrad
Expression, Ontogeny, and Regulation of Hypoxia-Inducible Transcription Factors in the Human Placenta
Biol Reprod,
August 1, 2000;
63(2):
559 - 569.
[Abstract]
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N. S. Chandel and P. T. Schumacker
Cellular oxygen sensing by mitochondria: old questions, new insight
J Appl Physiol,
May 1, 2000;
88(5):
1880 - 1889.
[Abstract]
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G. L. Semenza
HIF-1: mediator of physiological and pathophysiological responses to hypoxia
J Appl Physiol,
April 1, 2000;
88(4):
1474 - 1480.
[Abstract]
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S. H. Lee, P. L. Wolf, R. Escudero, R. Deutsch, S. W. Jamieson, and P. A. Thistlethwaite
Early Expression of Angiogenesis Factors in Acute Myocardial Ischemia and Infarction
N. Engl. J. Med.,
March 2, 2000;
342(9):
626 - 633.
[Abstract]
[Full Text]
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A. C. Koong, N. C. Denko, K. M. Hudson, C. Schindler, L. Swiersz, C. Koch, S. Evans, H. Ibrahim, Q. T. Le, D. J. Terris, et al.
Candidate Genes for the Hypoxic Tumor Phenotype
Cancer Res.,
February 1, 2000;
60(4):
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R. Wenger
Mammalian oxygen sensing, signalling and gene regulation
J. Exp. Biol.,
January 4, 2000;
203(8):
1253 - 1263.
[Abstract]
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M. V. Panchenko, H. W. Farber, and J. H. Korn
Induction of heme oxygenase-1 by hypoxia and free radicals in human dermal fibroblasts
Am J Physiol Cell Physiol,
January 1, 2000;
278(1):
C92 - C101.
[Abstract]
[Full Text]
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K. Zaman, H. Ryu, D. Hall, K. O'Donovan, K.-I Lin, M. P. Miller, J. C. Marquis, J. M. Baraban, G. L. Semenza, and R. R. Ratan
Protection from Oxidative Stress-Induced Apoptosis in Cortical Neuronal Cultures by Iron Chelators Is Associated with Enhanced DNA Binding of Hypoxia-Inducible Factor-1 and ATF-1/CREB and Increased Expression of Glycolytic Enzymes, p21waf1/cip1, and Erythropoietin
J. Neurosci.,
November 15, 1999;
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[Abstract]
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K. Maemura, C.-M. Hsieh, M. K. Jain, S. Fukumoto, M. D. Layne, Y. Liu, S. Kourembanas, S.-F. Yet, M. A. Perrella, and M.-E. Lee
Generation of a Dominant-negative Mutant of Endothelial PAS Domain Protein 1 by Deletion of a Potent C-terminal Transactivation Domain
J. Biol. Chem.,
October 29, 1999;
274(44):
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[Abstract]
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B. L. Ebert and H. F. Bunn
Regulation of the Erythropoietin Gene
Blood,
September 15, 1999;
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1864 - 1877.
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T. Hasegawa, L. Sorensen, H. Ooi, and B. C. Marshall
Decreased Intracellular Iron Availability Suppresses Epithelial Cell Surface Plasmin Generation . Transcriptional and Post-transcriptional Effects on u-PA and PAI-1 Expression
Am. J. Respir. Cell Mol. Biol.,
August 1, 1999;
21(2):
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[Abstract]
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L. E. Huang, W. G. Willmore, J. Gu, M. A. Goldberg, and H. F. Bunn
Inhibition of Hypoxia-inducible Factor 1 Activation by Carbon Monoxide and Nitric Oxide. IMPLICATIONS FOR OXYGEN SENSING AND SIGNALING
J. Biol. Chem.,
March 26, 1999;
274(13):
9038 - 9044.
[Abstract]
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E. S. Hanson, L. M. Foot, and E. A. Leibold
Hypoxia Post-translationally Activates Iron-regulatory Protein 2
J. Biol. Chem.,
February 19, 1999;
274(8):
5047 - 5052.
[Abstract]
[Full Text]
[PDF]
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J. F. O'Rourke, Y.-M. Tian, P. J. Ratcliffe, and C. W. Pugh
Oxygen-regulated and Transactivating Domains in Endothelial PAS Protein 1: Comparison with Hypoxia-inducible Factor-1alpha
J. Biol. Chem.,
January 22, 1999;
274(4):
2060 - 2071.
[Abstract]
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G. Camenisch, M. Tini, D. Chilov, I. Kvietikova, V. Srinivas, J. Caro, P. Spielmann, R. H. Wenger, and M. Gassmann
General applicability of chicken egg yolk antibodies: the performance of IgY immunoglobulins raised against the hypoxia-inducible factor 1{alpha}
FASEB J,
January 1, 1999;
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81 - 88.
[Abstract]
[Full Text]
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F. Agani and G. L. Semenza
Mersalyl Is a Novel Inducer of Vascular Endothelial Growth Factor Gene Expression and Hypoxia-Inducible Factor 1 Activity
Mol. Pharmacol.,
November 1, 1998;
54(5):
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[Abstract]
[Full Text]
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M.S. Wiesener, H. Turley, W.E. Allen, C. Willam, K.-U. Eckardt, K.L. Talks, S.M. Wood, K.C. Gatter, A.L. Harris, C.W. Pugh, et al.
Induction of Endothelial PAS Domain Protein-1 by Hypoxia: Characterization and Comparison With Hypoxia-Inducible Factor-1alpha
Blood,
October 1, 1998;
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2260 - 2268.
[Abstract]
[Full Text]
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L. E. Huang, J. Gu, M. Schau, and H. F. Bunn
Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway
PNAS,
July 7, 1998;
95(14):
7987 - 7992.
[Abstract]
[Full Text]
[PDF]
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C. H. Graham, T. E. Fitzpatrick, and K. R. McCrae
Hypoxia Stimulates Urokinase Receptor Expression Through a Heme Protein-Dependent Pathway
Blood,
May 1, 1998;
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3300 - 3307.
[Abstract]
[Full Text]
[PDF]
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E. S. Hanson and E. A. Leibold
Regulation of Iron Regulatory Protein 1 during Hypoxia and Hypoxia/Reoxygenation
J. Biol. Chem.,
March 27, 1998;
273(13):
7588 - 7593.
[Abstract]
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