Exposure to Selenomethionine and Selenocystine Induces Redox-Mediated ER Stress in Normal Breast Epithelial MCF-10A Cells
Résumé
Selenium is an essential trace element co-translationnaly incorporated into selenoproteins with
important biological functions. Health benefits have long been associated with selenium
supplementation. However, cytotoxicity is observed upon excessive selenium intake. The aim
of this study is to investigate the metabolic pathways underlying the response to the seleniumcontaining
amino acids selenomethionine and selenocysteine in a normal human breast
epithelial cell model. We show that both selenomethionine and selenocystine inhibit the
proliferation of non-cancerous MCF-10A cells in the same concentration range as cancerous
MCF-7 and Hela cells, which results in apoptotic cell death. Selenocystine exposure in MCF-
10A cells caused a severe depletion of free low molecular weight thiols, which might explain
the observed up-regulation of the expression of the oxidative stress pathway transcription factor
NRF2. Both selenomethionine and selenocystine induced the expression of target genes of the
unfolded protein response (GRP78, ATF4, CHOP). Using a redox-sensitive fluorescent probe
targeted to the endoplasmic reticulum (ER), we show that both selenoamino acids shifted the
ER redox balance towards an even more oxidizing environment. These results suggest that
alteration of the redox state of the ER may disrupt protein folding and cause ER stress-induced
apoptosis in MCF-10A cells exposed to selenoamino acids.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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