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Relevance of selenoprotein transcripts for selenium status in humans.

ABSTRACT: The most commonly used methods for assessing the selenium (Se) status in humans involve analysis of Se concentration, selenoprotein activity, and concentration in the blood and its compartments. Recently, it has been suggested that the expression of selenoprotein mRNA in circulating blood leukocytes could differently reflect Se status, due to prioritization of specific selenoprotein synthesis in response to dietary Se supply. Whereas the Se levels required for optimization of selenoprotein P level and plasma glutathione peroxidise activity are well known, estimation of Se level that is required for maximal mRNA expression of selenoprotein in humans is the subject of current investigations. Studies on rats suggest that whole blood selenoprotein mRNA level can be used as the relevant molecular biomarker for assessing Se status, and suboptimal Se intake may be sufficient to achieve effective expression. Human studies, however, did not confirm this hypothesis. According to studies on rodents and humans discussed in this review, it appears that suboptimal Se intake may be sufficient to satisfy molecular requirements of Se and it is lower than current recommended dietary intake in humans. The use of selenoprotein transcripts as a molecular biomarker of Se status requires further studies on a large group of healthy individuals with different baseline Se, including data regarding genetic polymorphism of selenoproteins and data regarding potential modifiers of Se metabolism.

SUBMITTER: Reszka E

PROVIDER: S-EPMC3316749 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Relevance of selenoprotein transcripts for selenium status in humans.

Reszka Edyta E Jablonska Ewa E Gromadzinska Jolanta J Wasowicz Wojciech W

Genes & nutrition 20110907 2

The most commonly used methods for assessing the selenium (Se) status in humans involve analysis of Se concentration, selenoprotein activity, and concentration in the blood and its compartments. Recently, it has been suggested that the expression of selenoprotein mRNA in circulating blood leukocytes could differently reflect Se status, due to prioritization of specific selenoprotein synthesis in response to dietary Se supply. Whereas the Se levels required for optimization of selenoprotein P lev ...[more]

PMID: 21898179

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Project description:Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

Dataset Information

Relevance of selenoprotein transcripts for selenium status in humans.

Publications

Relevance of selenoprotein transcripts for selenium status in humans.

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