Metal Ions as Activators of Hypoxia Inducible Factor
| Autor: | A. I. Osipyants, A. Yu. Khristichenko, N. A. Smirnova, Sergey Nikulin, Andrey A. Poloznikov, Irina G. Gazaryan, Vladimir I. Tishkov, A. A. Zakhariants |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
010405 organic chemistry Chemistry Metal ions in aqueous solution Cell General Chemistry 01 natural sciences 0104 chemical sciences Cell membrane Active center 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Hypoxia-inducible factors Transition metal Toxicity medicine Biophysics SN2 reaction |
| Zdroj: | Moscow University Chemistry Bulletin. 73:13-18 |
| ISSN: | 1935-0260 0027-1314 |
| DOI: | 10.3103/s0027131418020128 |
| Popis: | Activation of antihypoxic program under the action of a number of transition and heavy metals has been studied using cell-based HIF1 ODD-luc and HRE-luc reporters. It has been demonstrated that Au3+, Pb2+, Sn2+, Hg2+ are weak HIF1 ODD-luc activators, likely reflecting their weak competition for the ironbinding site in the active center of HIF prolyl hydroxylase. Metals capable of replacing iron–Mn2+, Zn2+, Cu2+ и Ni2+–activate at high submillimolar concentrations, which indicates low permeability of the cell membrane for transition metals. The highest activation is observed for Co2+ and Cd2+, however, Cd2+ is highly toxic even at 10 μM, in contrast to Co2+, which activates both reporters without toxicity signs up to 25 μM for 24 h. A significant activation by Co2+ is observed already in low micromolar range of concentrations, which can be recommended for use in hypoxia mimicking. |
| Databáze: | OpenAIRE |
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