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

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 PC...

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Bibliographic Details
Published in:Molecular biology (New York) 2022, Vol.56 (1), p.97-106
Main Authors: Mal’tseva, V. N., Goltyaev, M. V., Novoselov, S. V., Varlamova, E. G.
Format: Article
Language:English
Subjects:
Adenocarcinoma
AKT1 protein
Apoptosis
BAX protein
BIM protein
Biochemistry
Biomedical and Life Sciences
Breast
Cancer
Cell survival
Dithiothreitol
Endoplasmic reticulum
GADD34 protein
Human Genetics
Life Sciences
Molecular Cell Biology
Protein folding
Selenoproteins
Signal transduction
Sodium selenite
Transcription factors
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Summary: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.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893322010058