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A non-hypoxic, ROS-sensitive pathway mediates TNF-alpha-dependent regulation of HIF-1alpha.
- Source :
-
FEBS letters [FEBS Lett] 2001 Sep 14; Vol. 505 (2), pp. 269-74. - Publication Year :
- 2001
-
Abstract
- A non-hypoxic, reactive oxygen species (ROS)-sensitive pathway mediating tumor necrosis factor-alpha (TNF-alpha)-dependent regulation of hypoxia-inducible factor-1alpha (HIF-alpha) was investigated in vitro. TNF-alpha mediated the translocation of HIF-1alpha, associated with up-regulating its activity under normoxia. Analysis of the mode of action of TNF-alpha revealed the accumulation of hydrogen peroxide (H2O2), superoxide anion (O(2-.)) and hydroxyl radical (.OH). Antioxidants purported as prototypical scavengers of H2O2 and .OH, attenuated TNF-alpha-induced HIF-1alpha activation, and blockading NADPH-oxidase by scavenging O(2-.) reduced the activity of HIF-1alpha. Inhibition of the mitochondrion complex I abrogated TNF-alpha-dependent activation of HIF-1alpha. Interrupting the respiratory chain reversed the excitatory effect of TNF-alpha on HIF-1alpha. These results indicate a non-hypoxic pathway mediating cytokine-dependent regulation of HIF-1alpha in a ROS-sensitive mechanism.
- Subjects :
- Animals
Anions
Antioxidants pharmacology
Apoptosis
Cell Nucleus metabolism
Cells, Cultured
DNA metabolism
Dose-Response Relationship, Drug
Enzyme Activation
Fibroblasts metabolism
Hydrogen Peroxide pharmacology
Hypoxia
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Inflammation
Inhibitory Concentration 50
Mice
Mitochondria metabolism
Protein Transport
Recombinant Proteins metabolism
Time Factors
Up-Regulation
DNA-Binding Proteins metabolism
Nuclear Proteins metabolism
Reactive Oxygen Species metabolism
Transcription Factors
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-5793
- Volume :
- 505
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 11566189
- Full Text :
- https://doi.org/10.1016/s0014-5793(01)02833-2