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A. I. Osipyants, N. A. Smirnova, A. Yu. Khristichenko, S. V. Nikulin, A. A. Zakhariants, V. I. Tishkov, I. G. Gazaryan, A. A. Poloznikov
Metal ions as
activators of hypoxia inducible factor
Abstract
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 iron-binding 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.
Key words:
luciferase, reporter assay, transition metals, heavy metals, cobalt.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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