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Nrf2 target genes are induced under marginal selenium-deficiency.
Genes & Nutrition
|December 31, 2010
Summary
Suboptimal selenium intake in mice up-regulates antioxidant and phase II enzymes, particularly in the duodenum. This response aims to compensate for reduced selenoproteins and primes the cells for selenium repletion.
Area of Science:
- Nutritional Biochemistry
- Molecular Biology
- Genomics
Background:
- Suboptimal selenium supply is a concern in Europe, potentially impacting cellular functions.
- Previous studies indicated alterations in gene expression pathways under moderate selenium deficiency.
- Severe selenium deficiency is known to affect Nrf2-regulated adaptive response genes.
Purpose of the Study:
- To investigate changes in gene expression in response to suboptimal selenium intake.
- To identify specific genes and pathways involved in the adaptive response to low selenium.
- To explore the role of Nrf2-regulated genes in selenium deficiency.
Main Methods:
- Microarray analysis of mouse colon gene expression under adequate and moderately deficient selenium diets.
- Manual selection and confirmation of Nrf2 target genes using quantitative polymerase chain reaction (qPCR).
- Analysis of gene expression changes in the duodenum and colon.
Main Results:
- qPCR confirmed the induction of phase II enzymes (Nqo1, Gsts, Sult1b1, Ugt1a6) and antioxidant enzymes (Hmox1, Mt2, Prdx1, Srxn1, Sod1, Gclc) under a selenium-poor diet.
- Upregulation of these enzymes is interpreted as a compensatory mechanism for the loss of selenoproteins.
- The duodenum showed the strongest upregulation of antioxidant enzyme genes, including those for TrxR1 and GPx2, facilitating rapid translation upon selenium refeeding.
Conclusions:
- Moderate selenium deficiency triggers a compensatory upregulation of phase II and antioxidant enzymes, mediated by the Nrf2 pathway.
- Downregulation of GSK3β in selenium deficiency may contribute to Nrf2 pathway activation.
- The observed gene expression changes, particularly in the duodenum, suggest a protective and adaptive response to low selenium availability.
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