Abstract
Manganese (Mn) is crucially important for vital activity of cells and has many biological functions. Nevertheless, high doses of Mn taken up by an organism over a long period may cause neurodegenerative diseases such as manganism and Parkinsonism. The molecular mechanisms of this Mn toxicity are still poorly studied. It is now believed that Mn-induced pathophysiological neural processes are multifaceted and affect several metabolic pathways. In particular, Mn ions might affect the processes of DNA replication and repair. To test this possibility, we obtained an SKOV-3 cell line resistant to the toxic action of Mn ions. We found that these cells are characterized by the activation of poly(ADP-ribose)polymerase, which leads to increased ability to repair DNA. Thus, the model used here supports the suggestion that at least one cause of Mn cytotoxicity might be disorders of the processes involved in DNA replication and repair.
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Abbreviations
- DTT:
-
dithiothreitol
- misGvA:
-
misincorporation of G versus A
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- PAR:
-
poly(ADP-ribose)
- PARP-1:
-
poly(ADP-ribose)polymerase-1
- Pol ι:
-
DNA polymerase iota.
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Original Russian Text © K. A. Zakharcheva, L. V. Gening, K. Yu. Kazachenko, V. Z. Tarantul, 2017, published in Biokhimiya, 2017, Vol. 82, No. 1, pp. 101-110. Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-222, November 14, 2016.
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Zakharcheva, K.A., Gening, L.V., Kazachenko, K.Y. et al. Cells resistant to toxic concentrations of manganese have increased ability to repair DNA. Biochemistry Moscow 82, 38–45 (2017). https://doi.org/10.1134/S0006297917010047
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DOI: https://doi.org/10.1134/S0006297917010047