Abstract |
The molecular mechanisms by which cells detect hypoxia (1.5% O2), resulting in the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) protein remain unclear. One model proposes that mitochondrial generation of reactive oxygen species is required to stabilize HIF-1alpha protein. Primary evidence for this model comes from the observation that cells treated with complex I inhibitors, such as rotenone, or cells that lack mitochondrial DNA (rho(0)-cells) fail to generate reactive oxygen species or stabilize HIF-1alpha protein in response to hypoxia. In the present study, we investigated the role of mitochondria in regulating HIF-1alpha protein stabilization under anoxia (0% O2). Wild-type A549 and HT1080 cells stabilized HIF-1alpha protein in response to hypoxia and anoxia. The rho(0)-A549 cells and rho(0)-HT1080 cells failed to accumulate HIF-1alpha protein in response to hypoxia. However, both rho(0)-A549 and rho(0)-HT1080 were able to stabilize HIF-1alpha protein levels in response to anoxia. Rotenone inhibited hypoxic, but not anoxic, stabilization of HIF-1alpha protein. These results indicate that a functional electron transport chain is required for hypoxic but not anoxic stabilization of HIF-1alpha protein.
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Authors | Clara Schroedl, David S McClintock, G R Scott Budinger, Navdeep S Chandel |
Journal | American journal of physiology. Lung cellular and molecular physiology
(Am J Physiol Lung Cell Mol Physiol)
Vol. 283
Issue 5
Pg. L922-31
(Nov 2002)
ISSN: 1040-0605 [Print] United States |
PMID | 12376345
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Reactive Oxygen Species
- Recombinant Proteins
- Transcription Factors
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(metabolism)
- Animals
- Apoptosis
- Cell Hypoxia
(physiology)
- Cell Line
- Cricetinae
- Genes, Reporter
- Humans
- Hypoxia
(physiopathology)
- Hypoxia-Inducible Factor 1, alpha Subunit
- Kinetics
- Lung
- Mitochondria
(physiology)
- Oxygen Consumption
- Reactive Oxygen Species
(metabolism)
- Recombinant Proteins
(metabolism)
- Respiratory Mucosa
(physiology)
- Transcription Factors
(genetics, physiology)
- Transfection
- Urothelium
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