The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1
Abstract
The cardiovascular and respiratory systems play key roles in O 2 homeostasis. Physiological responses to hypoxia involve changes in gene expression that are mediated by the transcriptional activator hypoxia-inducible factor (HIF)-1. Analysis of mice heterozygous for a knockout allele at the locus encoding the O 2-regulated HIF-1α or HIF-2α subunit has revealed that these proteins are required for multiple physiological responses to chronic hypoxia, including erythrocytosis and pulmonary vascular remodeling. In mice with partial HIF-2α deficiency, hypoxia-induced expression of endothelin-1 and norepinephrine is dramatically impaired, and the mice fail to develop pulmonary hypertension after 4 wk of exposure to 10% O 2. In mice with partial HIF-1α deficiency, the ability of the carotid body to sense and/or respond to acute or chronic hypoxia is lost. In wild-type mice, brief episodes of intermittent hypoxia are sufficient to induce production of erythropoietin (EPO), which protects the heart against apoptosis after ischemia-reperfusion, whereas in mice with partial HIF-1α deficiency, intermittent hypoxia does not induce EPO production or cardiac protection. Parenteral administration of EPO to rodents is sufficient to induce dramatic protection against ischemia-reperfusion injury in the heart. Thus HIF-1 mediates critical physiological responses to hypoxia, and the elucidation of these homeostatic mechanisms may lead to novel therapies for the most common causes of mortality in the US population.
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Cites
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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Self-citationPurification and Characterization of Hypoxia-inducible Factor 1
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Self-citationHIF‐1α is required for solid tumor formation and embryonic vascularization
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Cited by
How mitochondria produce reactive oxygen species
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HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
Oxygen, oxidative stress, hypoxia, and heart failure
Giordano, F. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524408 · Cited by 1,496
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Metadata
- Authors
- Semenza, G. L.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2004-03
- Volume
- 96
- Issue
- 3
- Pages
- 1173-1177
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2030319693
- Cited by
- 268
- References
- 49
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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