Cobalt induces hypoxia-inducible factor-1 alpha (HIF-1 alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism
dc.creator | Triantafyllou, A. | en |
dc.creator | Liakos, P. | en |
dc.creator | Tsakalof, A. | en |
dc.creator | Georgatsou, E. | en |
dc.creator | Simos, G. | en |
dc.creator | Bonanou, S. | en |
dc.date.accessioned | 2015-11-23T10:50:21Z | |
dc.date.available | 2015-11-23T10:50:21Z | |
dc.date.issued | 2006 | |
dc.identifier | 10.1080/10715760600730810 | |
dc.identifier.issn | 1071-5762 | |
dc.identifier.uri | http://hdl.handle.net/11615/33713 | |
dc.description.abstract | The iron-chelator desferrioxamine (DFO) and the transition metal cobalt induce hypoxia-inducible factor-1 alpha (HIF-1 alpha) in normoxia. DFO stabilizes HIF-1 alpha from proteolysis by inhibiting the activity of iron-dependent prolyl hydroxylases, but the mechanism of action of cobalt is not fully elucidated. The purpose of this study was to examine the regulation of HIF-1 alpha induction and HeLa cell proliferation by cobalt and the role of iron in these processes. Our results show that, unlike DFO, induction of transcriptionally active HIF-1 alpha by CoCl2 cannot be abrogated by the addition of excess Fe3+, but involves the production of reactive oxygen species (ROS) and the operation of the phosphatidylinositol-3 kinase (PI-3K) and MAPK pathways. CoCl2, as well as DFO, decreased HeLa cell proliferation, but these effects were reversed by the addition of Fe3+. We conclude that the effect of cobalt on cell proliferation is iron-dependent, while its effects on HIF-1 alpha induction are ROS- and signaling pathways-dependent, but iron-independent. | en |
dc.source | Free Radical Research | en |
dc.source.uri | <Go to ISI>://WOS:000240093600008 | |
dc.subject | hypoxia | en |
dc.subject | hypoxia-inducible factor-1 | en |
dc.subject | cobalt | en |
dc.subject | iron | en |
dc.subject | desferrioxamine | en |
dc.subject | HeLa | en |
dc.subject | cell proliferation | en |
dc.subject | HYPOXIA-INDUCIBLE FACTOR | en |
dc.subject | UBIQUITIN-PROTEASOME PATHWAY | en |
dc.subject | TRANSCRIPTION | en |
dc.subject | FACTORS | en |
dc.subject | SIGNAL-TRANSDUCTION | en |
dc.subject | FACTOR 1-ALPHA | en |
dc.subject | HIF-ALPHA | en |
dc.subject | TUMOR | en |
dc.subject | ANGIOGENESIS | en |
dc.subject | INDUCED APOPTOSIS | en |
dc.subject | OXIDATIVE STRESS | en |
dc.subject | GENE-EXPRESSION | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.title | Cobalt induces hypoxia-inducible factor-1 alpha (HIF-1 alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism | en |
dc.type | journalArticle | en |
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