Article Dans Une Revue Biological Trace Element Research Année : 2024

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.
Fichier principal
Vignette du fichier
BTER accepted manuscript.pdf (1.9 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04903940 , version 1 (21-01-2025)

Identifiants

Citer

Marc Dauplais, Stephane Romero, Myriam Lazard. Exposure to Selenomethionine and Selenocystine Induces Redox-Mediated ER Stress in Normal Breast Epithelial MCF-10A Cells. Biological Trace Element Research, 2024, ⟨10.1007/s12011-024-04244-y⟩. ⟨hal-04903940⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More