A T/C polymorphism in the GPX4 3'UTR affects the selenoprotein expression pattern and cell viability in transfected Caco-2 cells.
Biochim Biophys Acta
; 1810(6): 584-91, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21459128
ABSTRACT
BACKGROUND:
Synthesis of selenoproteins such as glutathione peroxidases (GPx) requires a specific tRNA and a stem-loop structure in the 3'untranslated region (3'UTR) of the mRNA. A common single nucleotide polymorphism occurs in the GPX4 gene in a region corresponding to the 3'UTR.METHODS:
The two variant 3'UTR sequences were linked to sequences from a selenoprotein reporter gene (iodothyronine deiodinase) and expressed in Caco-2 cells. Clones expressing comparable levels of deiodinase (assessed by real-time PCR) were selected and their response to tert-butyl hydroperoxide assessed by cell viability and measurement of reactive oxygen species. Selenoprotein expression was assessed by real-time PCR, enzyme activity and immunoassay.RESULTS:
When selenium supply was low, cells overexpressing the C variant 3'UTR showed lower viability after oxidative challenge, increased levels of reactive oxygen species and lower GPx activity and SelH mRNA expression compared to cells overexpressing the T variant. After selenium supplementation, cell viability and GPx4 expression were higher in the cells overexpressing the C variant. Expression of transgenes incorporating the T/C variant GPX4 (rs713041) sequences in Caco-2 cells leads to alterations in both cell viability after an oxidative challenge and selenoprotein expression. This suggests that the two variants compete differently in the selenoprotein hierarchy. GENERALSIGNIFICANCE:
The data provide evidence that the T/C variant GPX4 (rs713041) alters the pattern of selenoprotein synthesis if selenium intake is low. Further work is required to assess the impact on disease susceptibility.
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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Regulação Enzimológica da Expressão Gênica
/
Selenoproteínas
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Glutationa Peroxidase
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article