Metal Ions as Activators of Hypoxia Inducible Factor

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 Au 3+ , Pb 2+ , Sn 2+ , Hg 2+ are weak HIF1 ODD-luc activators, likely reflecting their weak competition f...

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Bibliographic Details
Published in:Moscow University chemistry bulletin 2018, Vol.73 (1), p.13-18
Main Authors: Osipyants, A. I., Smirnova, N. A., Khristichenko, A. Yu, Nikulin, S. V., Zakhariants, A. A., Tishkov, V. I., Gazaryan, I. G., Poloznikov, A. A.
Format: Article
Language:English
Subjects:
Activation
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Cobalt
Copper
Heavy metals
Hypoxia
Lead
Mercury (metal)
Toxicity
Transition metals
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Summary: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 Au 3+ , Pb 2+ , Sn 2+ , Hg 2+ 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–Mn 2+ , Zn 2+ , Cu 2+ и Ni 2+ –activate at high submillimolar concentrations, which indicates low permeability of the cell membrane for transition metals. The highest activation is observed for Co 2+ and Cd 2+ , however, Cd 2+ is highly toxic even at 10 μM, in contrast to Co 2+ , which activates both reporters without toxicity signs up to 25 μM for 24 h. A significant activation by Co 2+ is observed already in low micromolar range of concentrations, which can be recommended for use in hypoxia mimicking.
ISSN:0027-1314
1935-0260
DOI:10.3103/S0027131418020128