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
Ημερομηνία
2006Λέξη-κλειδί
Επιτομή
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.
Collections
Related items
Showing items related by title, author, creator and subject.
-
Hypoxia-induced Changes in SUMO Conjugation Affect Transcriptional Regulation under Low Oxygen
Chachami G., Stankovic-Valentin N., Karagiota A., Basagianni A., Plessmann U., Urlaub H., Melchior F., Simos G. (2019)Hypoxia occurs in pathological conditions, such as cancer, as a result of the imbalance between oxygen supply and consumption by proliferating cells. HIFs are critical molecular mediators of the physiological response to ... -
Reoxygenation induces reactive oxygen species production and ferroptosis in renal tubular epithelial cells by activating aryl hydrocarbon receptor
Eleftheriadis T., Pissas G., Filippidis G., Liakopoulos V., Stefanidis I. (2021)During the reperfusion phase of ischemia‑reper‑ fusion injury, reactive oxygen species (ROS) production aggravates the course of many diseases, including acute kidney injury. Among the various enzymes implicated in ROS ... -
The flavonoid quercetin induces hypoxia-inducible factor-1 alpha (HIF-1 alpha) and inhibits cell proliferation by depleting intracellular iron
Triantafyllou, A.; Liakos, P.; Tsakalof, A.; Chachami, G.; Paraskeva, E.; Molyvdas, P. A.; Georgatsou, E.; Simos, G.; Bonanou, S. (2007)Quercetin, a flavonoid with anti- oxidant, metal chelating, kinase modulating and anti- proliferative properties, can induce hypoxia- inducible factor-1 alpha (HIF-1 alpha) in normoxia, but its mechanism of action has not ...