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Metal Ions as Activators of Hypoxia Inducible Factor

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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Moscow University Chemistry Bulletin Springer Journals

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Allerton Press, Inc.
Subject
Chemistry; Chemistry/Food Science, general
ISSN
0027-1314
eISSN
1935-0260
DOI
10.3103/S0027131418020128
Publisher site
See Article on Publisher Site

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 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.

Journal

Moscow University Chemistry BulletinSpringer Journals

Published: May 30, 2018

References