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Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.

Tsuji PA, Carlson BA, Anderson CB, Seifried HE, Hatfield DL, Howard MT - Nutrients (2015)

Bottom Line: Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ.Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver.These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, MD, 21252, USA. ptsuji@towson.edu.

ABSTRACT
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

No MeSH data available.


Related in: MedlinePlus

Analyses of ribosome footprint (RPF) distribution on RefSeq and selenoprotein mRNAs. (A) 0 ppm Se and (B) 0.1 ppm Se samples. RPF 5′ ends were aligned to all RefSeq mRNAs with coding DNA sequences (CDSs) > 400 nts and their positions relative to the start codon (0 position, left hand side) and stop codon (0 position, right hand side) were determined. The fraction of RPF 5′ ends aligning to nts −50 to +70, relative to RefSeq start codons, and nts −70 to +35, relative to RefSeq stop codons (0 position, right hand side), are shown. Distinct 3nt periodicity can be seen starting 13 nts upstream of start codons and ending 16 nts upstream of stop codons indicating that the first nucleotide of the A-site codon is located ~16 nts downstream of the 5′ end of the RPFs. Y-axis represents the fraction of reads covering each nucleotide summed for all aligned RefSeq mRNAs (CDS > 400 nts). (C) The fraction of RPFs with 5′ ends mapping to the first, second, or third codon position for CDSs and UTRs of RefSeq mRNAs. For UTRs, the first, second, and third “codon” position were determined relative to the CDS reading frame. (D) The 5′ end of RPFs from the 0 ppm Se or 0.1 ppm Se samples were aligned to selenoprotein mRNAs. The fraction of RPF 5′ ends that aligned to codon positions 1, 2, or 3 upstream (5′ RPFs) or downstream (3′ RPFs) of the UGA-Sec codon is shown.
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nutrients-07-05297-f002: Analyses of ribosome footprint (RPF) distribution on RefSeq and selenoprotein mRNAs. (A) 0 ppm Se and (B) 0.1 ppm Se samples. RPF 5′ ends were aligned to all RefSeq mRNAs with coding DNA sequences (CDSs) > 400 nts and their positions relative to the start codon (0 position, left hand side) and stop codon (0 position, right hand side) were determined. The fraction of RPF 5′ ends aligning to nts −50 to +70, relative to RefSeq start codons, and nts −70 to +35, relative to RefSeq stop codons (0 position, right hand side), are shown. Distinct 3nt periodicity can be seen starting 13 nts upstream of start codons and ending 16 nts upstream of stop codons indicating that the first nucleotide of the A-site codon is located ~16 nts downstream of the 5′ end of the RPFs. Y-axis represents the fraction of reads covering each nucleotide summed for all aligned RefSeq mRNAs (CDS > 400 nts). (C) The fraction of RPFs with 5′ ends mapping to the first, second, or third codon position for CDSs and UTRs of RefSeq mRNAs. For UTRs, the first, second, and third “codon” position were determined relative to the CDS reading frame. (D) The 5′ end of RPFs from the 0 ppm Se or 0.1 ppm Se samples were aligned to selenoprotein mRNAs. The fraction of RPF 5′ ends that aligned to codon positions 1, 2, or 3 upstream (5′ RPFs) or downstream (3′ RPFs) of the UGA-Sec codon is shown.

Mentions: Assessment of ribosome footprints aligned to all RefSeq mRNAs revealed that the footprints were highly enriched in coding DNA sequences (CDS) relative to UTRs (Figure 2A,B), and were positioned with a strong triplet phasing corresponding to the expected codon step size of actively translating ribosomes (Figure 2C). Likewise, triplet phasing was observed for the ribosome footprints located upstream and downstream of UGA-Sec codons in the selenoprotein mRNAs (Figure 2D) demonstrating that the ribonuclease resistant fragments obtained from selenoprotein mRNAs have the expected features of footprints obtained from actively translating ribosomes.


Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.

Tsuji PA, Carlson BA, Anderson CB, Seifried HE, Hatfield DL, Howard MT - Nutrients (2015)

Analyses of ribosome footprint (RPF) distribution on RefSeq and selenoprotein mRNAs. (A) 0 ppm Se and (B) 0.1 ppm Se samples. RPF 5′ ends were aligned to all RefSeq mRNAs with coding DNA sequences (CDSs) > 400 nts and their positions relative to the start codon (0 position, left hand side) and stop codon (0 position, right hand side) were determined. The fraction of RPF 5′ ends aligning to nts −50 to +70, relative to RefSeq start codons, and nts −70 to +35, relative to RefSeq stop codons (0 position, right hand side), are shown. Distinct 3nt periodicity can be seen starting 13 nts upstream of start codons and ending 16 nts upstream of stop codons indicating that the first nucleotide of the A-site codon is located ~16 nts downstream of the 5′ end of the RPFs. Y-axis represents the fraction of reads covering each nucleotide summed for all aligned RefSeq mRNAs (CDS > 400 nts). (C) The fraction of RPFs with 5′ ends mapping to the first, second, or third codon position for CDSs and UTRs of RefSeq mRNAs. For UTRs, the first, second, and third “codon” position were determined relative to the CDS reading frame. (D) The 5′ end of RPFs from the 0 ppm Se or 0.1 ppm Se samples were aligned to selenoprotein mRNAs. The fraction of RPF 5′ ends that aligned to codon positions 1, 2, or 3 upstream (5′ RPFs) or downstream (3′ RPFs) of the UGA-Sec codon is shown.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4555136&req=5

nutrients-07-05297-f002: Analyses of ribosome footprint (RPF) distribution on RefSeq and selenoprotein mRNAs. (A) 0 ppm Se and (B) 0.1 ppm Se samples. RPF 5′ ends were aligned to all RefSeq mRNAs with coding DNA sequences (CDSs) > 400 nts and their positions relative to the start codon (0 position, left hand side) and stop codon (0 position, right hand side) were determined. The fraction of RPF 5′ ends aligning to nts −50 to +70, relative to RefSeq start codons, and nts −70 to +35, relative to RefSeq stop codons (0 position, right hand side), are shown. Distinct 3nt periodicity can be seen starting 13 nts upstream of start codons and ending 16 nts upstream of stop codons indicating that the first nucleotide of the A-site codon is located ~16 nts downstream of the 5′ end of the RPFs. Y-axis represents the fraction of reads covering each nucleotide summed for all aligned RefSeq mRNAs (CDS > 400 nts). (C) The fraction of RPFs with 5′ ends mapping to the first, second, or third codon position for CDSs and UTRs of RefSeq mRNAs. For UTRs, the first, second, and third “codon” position were determined relative to the CDS reading frame. (D) The 5′ end of RPFs from the 0 ppm Se or 0.1 ppm Se samples were aligned to selenoprotein mRNAs. The fraction of RPF 5′ ends that aligned to codon positions 1, 2, or 3 upstream (5′ RPFs) or downstream (3′ RPFs) of the UGA-Sec codon is shown.
Mentions: Assessment of ribosome footprints aligned to all RefSeq mRNAs revealed that the footprints were highly enriched in coding DNA sequences (CDS) relative to UTRs (Figure 2A,B), and were positioned with a strong triplet phasing corresponding to the expected codon step size of actively translating ribosomes (Figure 2C). Likewise, triplet phasing was observed for the ribosome footprints located upstream and downstream of UGA-Sec codons in the selenoprotein mRNAs (Figure 2D) demonstrating that the ribonuclease resistant fragments obtained from selenoprotein mRNAs have the expected features of footprints obtained from actively translating ribosomes.

Bottom Line: Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ.Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver.These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, MD, 21252, USA. ptsuji@towson.edu.

ABSTRACT
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

No MeSH data available.


Related in: MedlinePlus