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.
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Abbreviations
- HIF:
-
hypoxia inducible factor
- HRE:
-
hypoxia response element
- PHD:
-
prolyl hydroxylase
- pVHL:
-
von Hippel-Lindau protein
References
Rose, N.R., McDonough, M.A., King, O.N.F., Kawamura, A., and Schofield, C.J., Chem. Soc. Rev., 2011, vol. 40, p. 4364.
Semenza, G.L. and Wang, G.L., Mol. Cell. Biol., 1992, vol. 12, p. 5447.
Wang, G.L. and Semenza, G.L., J. Biol. Chem., 1993, vol. 268, p. 21513.
Bruick, R.K. and McKnight, S.L., Science, 2001, vol. 294, p. 1337.
Semenza, G.L., Jiang, B.H., Leung, S.W., Passantino, R., Concordet, J.P., Maire, P., and Giallongo, A., J. Biol. Chem., 1996, vol. 271, p. 32529.
Smirnova, N.A., Haskew-Layton, R.E., Basso, M., Hushpulian, D.M., Payappilly, J.B., Speer, R.E., Ahn, Y.H., Rakhman, I., Cole, P.A., Pinto, J.T., Ratan, R.R., and Gazaryan, I.G., Chem. Biol., 2011, vol. 18, p. 752.
Smirnova, N.A., Rakhman, I., Moroz, N., Basso, M., Payappilly, J., Kazakov, S., Hernandez-Guzman, F., Gaisina, I.N., Kozikowski, A.P., Ratan, R.R., and Gazaryan, I.G., Chem. Biol., 2010, vol. 17, p. 380.
Smirnova, N.A., Kaidery, N.A., Hushpulian, D.M., Rakhman, I.I., Poloznikov, A.A., Tishkov, V.I., Karuppagounder, S.S., Gaisina, I.N., Pekcec, A., Leyen, K.V., Kazakov, S.V., Yang, L., Thomas, B., Ratan, R.R., and Gazaryan, I.G., Aging Dis., 2016, vol. 7, p. 745.
Ma, T.C., Langley, B., Ko, B., Wei, N., Gazaryan, I.G., Zareen, N., Yamashiro, D.J., Willis, D.E., and Ratan, R.R., Neurobiol. Dis., 2013, vol. 49, p. 13.
Kasten, U., Hartwig, A., and Beyersmann, D., Arch.Toxicol., 1992, vol. 66, p. 592.
Permenter, M.G., Dennis, W.E., Sutto, T.E., Jackson, D.A., Lewis, J.A., and Stallings, J.D., PLoS One, 2013, vol. 8.
Malard, V., Berenguer, F., Prat, O., Ruat, S., Steinmetz, G., and Quemeneur, E., BMC Genomics, 2007, vol. 8, p. 147.
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Original Russian Text © A.I. Osipyants, N.A. Smirnova, A.Yu. Khristichenko, S.V. Nikulin, A.A. Zakhariants, V.I. Tishkov, I.G. Gazaryan, A.A. Poloznikov, 2018, published in Vestnik Moskovskogo Universiteta, Seriya 2: Khimiya, 2018, No. 2, pp. 85–91.
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Osipyants, A.I., Smirnova, N.A., Khristichenko, A.Y. et al. Metal Ions as Activators of Hypoxia Inducible Factor. Moscow Univ. Chem. Bull. 73, 13–18 (2018). https://doi.org/10.3103/S0027131418020128
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DOI: https://doi.org/10.3103/S0027131418020128