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Effects of Sodium Selenite and Dithiothreitol on Expression of Endoplasmic Reticulum Selenoproteins and Apoptosis Markers in MSF7 Breast Adenocarcinoma Cells

  • MOLECULAR CELL BIOLOGY
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Abstract

The endoplasmic reticulum (ER) stress inducers dithiothreitol (DTT) and sodium selenite (SS) were tested for effect on expression of ER selenoproteins and apoptosis markers in MCF7 breast adenocarcinoma cells. DTT used at 1 or 5 mM did not affect the survival of MCF7 cells. Based on the real-time PCR data and the protein expression levels of ER stress markers, ER stress was assumed to evolve along an adaptation pathway in MCF7 cells treated with 1 or 5 mM DTT, involving mainly the transcription factors IRE1 and ATF6 and the selenoproteins SELS, SELK, SELT, SELM, and SELN. Cell treatment with 0.01 μM SS decreases the mRNA levels of all genes examined. When the SS concentration was increased to 0.1 μM, an increase in expression was observed for key ER stress genes and apoptosis markers, including CHOP, GADD34, PUMA, BIM, ATF4, sXBP, uXBP, AKT1, BAX, and BAK. Higher SS concentrations were assumed to trigger the unfolded protein response (UPR) via a proapoptic signaling pathway involving PERK and an alternative IRE1 signaling pathway. Used at 1 μM, SS increased the mRNA levels of apoptosis markers, upregulated expression of a spliced form of XBP1, and substantially decreased the cell survival. SS (1 μM) was assumed to trigger apoptosis in MCF7 cells. The results indicate that both adaptive and proapoptic UPR signaling pathways are activated in cells, depending on the nature and concentration of the ER stress inducer.

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ACKNOWLEDGMENTS

We are grateful to the Department of Optical Microscopy and Spectrophotometry (Pushchino Biological Research Center, Russian Academy of Sciences, http://www.ckp-rf.ru/ckp/670266/).

Funding

This work was supported by State Contract no. 0191-2019-0019.

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  1. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    V. N. Mal’tseva, M. V. Goltyaev, S. V. Novoselov & E. G. Varlamova

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  1. V. N. Mal’tseva
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  2. M. V. Goltyaev
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  3. S. V. Novoselov
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Correspondence to V. N. Mal’tseva.

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Translated by T. Tkacheva

Abbreviations: ASK1, apoptosis signal-regulating kinase 1; ATF4 and ATF6, activating transcription factors 4 and 6, respectively; Bak, Bax, and Bim, apoptosis inducers of the Bcl-2 family; CHOP, CCAAT enhancer-binding protein homologous protein; DIO2, iodothyronine deiodinase 2; IRE1, inositol-requiring enzyme 1; GADD34, growth arrest and DNA damage-inducible protein 34; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PUMA, p53 upregulated modulator of apoptosis; SELK, SELN, SELS, SELM, SELT, SELI, and SEP15, selenoproteins K, N, S, M, T, I, and 15, respectively; UPR, unfolded protein response; XBP1, X-box binding protein 1; ROS, reactive oxygen species; DTT, dithiothreitol; SS, sodium selenite; REL, relative expression level; PCR, polymerase chain reaction; ER, endoplasmic reticulum.

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Mal’tseva, V.N., Goltyaev, M.V., Novoselov, S.V. et al. Effects of Sodium Selenite and Dithiothreitol on Expression of Endoplasmic Reticulum Selenoproteins and Apoptosis Markers in MSF7 Breast Adenocarcinoma Cells. Mol Biol 56, 97–106 (2022). https://doi.org/10.1134/S0026893322010058

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