The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Hypoxia-inducible Factor-1 Mediates Transcriptional Activation of the Heme Oxygenase-1 Gene in Response to Hypoxia
Open accessAbstract
Exposure of rats to hypoxia (7% O2) markedly increased the level of heme oxygenase-1 (HO-1) mRNA in several tissues. Accumulation of HO-1 transcripts was also observed after exposure of rat aortic vascular smooth muscle (VSM) cells to 1% O2, and this induction was dependent on gene transcription. Activation of the mouse HO-1 gene by all agents thus far tested is mediated by two 5'-enhancer sequences, SX2 and AB1, but neither fragment was responsive to hypoxia in VSM cells. Hypoxia-dependent induction of the chloramphenicol acetyltransferase (CAT) reporter gene was mediated by a 163-bp fragment located approximately 9.5 kilobases upstream of the transcription start site. This fragment contains two potential binding sites for hypoxia-inducible factor 1 (HIF-1). A role for HIF-1 in HO-1 gene regulation was established by the following observations: 1) HIF-1 specifically bound to an oligonucleotide spanning these sequences, 2) mutation of these sequences abolished HIF-1 binding and hypoxia-dependent gene activation in VSM cells, 3) hypoxia increased HIF-1alpha and HIF-1beta protein levels in VSM cells, and 4) hypoxia-dependent HO-1 mRNA accumulation was not observed in mutant hepatoma cells lacking HIF-1 DNA-binding activity. Taken together, these data demonstrate that hypoxia induces HO-1 expression in animal tissues and cell cultures and implicate HIF-1 in this response.
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“Other bona fide HIF-regulated genes involved in iron metabolism include transferrin, which transports serum iron in its ferric form (Fe3+), its high affinity receptor TFR1, 183–185 ceruloplasmin, which oxidizes Fe2+ to Fe3+ and is important for iron transport, 186 and heme-oxygenase-1, which is critical for the recycling of iron from phagocytosed erythrocytes.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [186]
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“Other bona fide HIF-regulated genes involved in iron metabolism include transferrin, which transports serum iron in its ferric form (Fe3+), its high affinity receptor TFR1, 183–185 ceruloplasmin, which oxidizes Fe2+ to Fe3+ and is important for iron transport, 186 and heme-oxygenase-1, which is critical for the recycling of iron from phagocytosed erythrocytes.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [187]
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Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
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Self-citationVascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis
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Self-citationPurification and Characterization of Hypoxia-inducible Factor 1
Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094
Self-citationTranscriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Self-citationCell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803
General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4304 · Cited by 1,468
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Self-citationTranscriptional Regulation of the Rat Vascular Endothelial Growth Factor Gene by Hypoxia
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Cited by
Sorted by citations
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Ryter, S. W., Alam, J., & Choi, A. M. K. (2006) · Physiological Reviews · doi:10.1152/physrev.00011.2005 · Cited by 2,346
Self-citationRegulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914
Self-citationHIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Self-citationHypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,690
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Metadata
- Authors
- Lee, P. J., Jiang, B.-H., Chin, B. Y., Iyer, N. V., Alam, J., Semenza, G. L., & Choi, A. K.
- Affiliations
- Johns Hopkins University (US)
- Ochsner Medical Center (US)
- Corresponding author
- Alam, Jawed
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-02
- Volume
- 272
- Issue
- 9
- Pages
- 5375-5381
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2081635255
- Cited by
- 782
- References
- 50
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 26 · 2023: 17 · 2022: 22 · 2021: 27 · 2020: 31 · 2019: 21 · 2018: 14 · 2017: 17 · 2016: 19 · 2015: 16 · 2014: 18 · 2013: 28 · 2012: 21
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5k11ag000516-03, 5r01dk043135-07)
- National Institute on Aging
- National Heart, Lung, and Blood Institute (R01HL055338)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- HIF-1, heme oxygenase-1, hypoxia, transcriptional activation, vascular smooth muscle cells, HIF-1α, ARNT, promoter regulation, hepatoma cells, oxygen deprivation
- MeSH terms
- Animals, Hypoxia, Base Sequence, Dactinomycin, DNA-Binding Proteins, Heme Oxygenase (Decyclizing), Molecular Sequence Data, Muscle, Smooth, Vascular, Nuclear Proteins, RNA, Messenger, Transcription Factors, Restriction Mapping, Transcriptional Activation, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Helix-Loop-Helix Motifs, Mice, Rats, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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