Nrf2 target genes are induced under marginal selenium-deficiency

Abstract

A suboptimal selenium supply appears to prevail in Europe. The current study, therefore, was focused on the changes in gene expression under a suboptimal selenium intake. Previous microarray analyses in the colon of mice fed either a selenium-adequate or a moderately deficient diet revealed a change in genes of several pathways. Severe selenium-deficiency has been found previously to influence Nrf2-regulated genes of the adaptive response. Since the previous pathway analyses were done with a program not searching for Nrf2 target genes, respective genes were manually selected and confirmed by qPCR. qPCR revealed an induction of phase II (Nqo1, Gsts, Sult1b1 and Ugt1a6) and antioxidant enzymes (Hmox1, Mt2, Prdx1, Srxn1, Sod1 and Gclc) under the selenium-poor diet, which is considered to compensate for the loss of selenoproteins. The strongest effects were observed in the duodenum where preferentially genes for antioxidant enzymes were up-regulated. These also include the mRNA of the selenoproteins TrxR1 and GPx2 that would enable their immediate translation upon selenium refeeding. The down-regulation of Gsk3b in moderate selenium-deficiency observed in the previous paper provides a possible explanation for the activation of the Nrf2 pathway, because inhibition of GSK3b results in the nuclear accumulation of Nrf2.

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

“…In addition, decreased in these tissues were mRNAs for inflammatory pathways, including tumor necrosis factor a (TNF-a) and interleukin 2 (IL-2). Interestingly, marginal Se deficiency (0.08 ppm Se) actually upregulated mRNA for Txnrd1 and Gpx2 in duodenum, thus suggesting that these mRNAs may be most abundant in the pool of selenoprotein mRNAs and first to become translated once the tissue is restored to Se-replete conditions (178). In humans who were supplemented with 100 lg/day Se as sodium selenite for 6 weeks, microarrays were used to analyze peripheral lymphocytes and the main pathways affected were those involving increased ribosomal protein and translation factor gene expression (192).…”

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

“…High-throughput genomic techniques such as gene microarrays provide a new approach to identify novel targets of Se and to integrate them into key pathways and networks. Using such transcriptomics methods, the pattern of gene expression changes has been examined in response to altered Se supply in the mouse, in response to Se supplementation in human subjects and in response to altered Se supply in cell culture (48)(49)(50)(51)(52)(53) .…”

Protective Effects of omega-3 fatty acids and/ or Nano- selenium on Cisplatin and Ionizing radiation induced liver toxicity in rats

“…46 selenium compounds or its metabolites may directly activate the Nrf2 pathway by modifying critical thiols in Keap1. 47 Nrf2 activators might be a successful strategy to control disease, which is associated with oxidative injuries. 48 Consequently, in the current study the tested combination of both FO and SeNPs may reveal the totality of efficiency of either compound alone; as they act by more than one mechanism.…”