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The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply.

Hoffmann PR, Höge SC, Li PA, Hoffmann FW, Hashimoto AC, Berry MJ - Nucleic Acids Res. (2007)

Bottom Line: Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway.Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes.We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. peterh@pbrc.hawaii.edu

ABSTRACT
Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key role in selenium (Se) transport throughout the body. Development of a Sel P knockout mouse model has supported this notion and initial studies have indicated that selenium supply to various tissues is differentially affected by genetic deletion of Sel P. Se in the form of the amino acid, selenocysteine, is incorporated into selenoproteins at UGA codons. Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in mice affected levels of the mRNAs encoding all known members of the murine selenoprotein family, as well as three non-selenoprotein factors involved in their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2 (SBP2) and SECp43. Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes. We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

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Comparison of Sel P knockout to wild-type mice for abundance of mRNA for selenoproteins, selenoprotein-synthesis factors and housekeeping genes. Total RNA was extracted from heart (A), lung (B), brain (C), and testes (D), which were used for cDNA synthesis and real-time PCR analysis. Levels of each target mRNA relative to hprt are shown for each tissue and grouped into either low copy (average <0.5) on the left, medium copy (average 0.5–10) in the middle and high copy (average >10) on the right. Black bars represent wild-type mice and white bars represent Sel P knockout mice. Number of mice used for each wild-type tissue were, 4 (brain and testes), 5 (heart) or 6 (lung) and for all 3 knockout tissues. Results represent mean +SE.
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Figure 2: Comparison of Sel P knockout to wild-type mice for abundance of mRNA for selenoproteins, selenoprotein-synthesis factors and housekeeping genes. Total RNA was extracted from heart (A), lung (B), brain (C), and testes (D), which were used for cDNA synthesis and real-time PCR analysis. Levels of each target mRNA relative to hprt are shown for each tissue and grouped into either low copy (average <0.5) on the left, medium copy (average 0.5–10) in the middle and high copy (average >10) on the right. Black bars represent wild-type mice and white bars represent Sel P knockout mice. Number of mice used for each wild-type tissue were, 4 (brain and testes), 5 (heart) or 6 (lung) and for all 3 knockout tissues. Results represent mean +SE.

Mentions: Results from our comparisons are displayed in Figure 2 and reveal several interesting features regarding how genetic deletion of Sel P affects different tissues. First, both testes and brain displayed overall decreases in selenoprotein mRNA abundance as well as decreases in housekeeping mRNAs. Although statistical significance was not achieved for most of the mRNAs due to variability and low numbers of mice per group (N = 3 − 6), the brain and testes were clearly more affected than heart and lung. This was particularly evident for mRNAs for the medium and high copy genes and may reflect apoptotic or necrotic cellular damage, which may be involved in or lead to the physiological problems in these tissues. In contrast, in heart and lung mRNA abundance was decreased only in a small number of selenoproteins expressed in the low copy group. The medium and high copy selenoprotein mRNAs in heart and lung are much less affected by genetic deletion of Sel P.Figure 2.


The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply.

Hoffmann PR, Höge SC, Li PA, Hoffmann FW, Hashimoto AC, Berry MJ - Nucleic Acids Res. (2007)

Comparison of Sel P knockout to wild-type mice for abundance of mRNA for selenoproteins, selenoprotein-synthesis factors and housekeeping genes. Total RNA was extracted from heart (A), lung (B), brain (C), and testes (D), which were used for cDNA synthesis and real-time PCR analysis. Levels of each target mRNA relative to hprt are shown for each tissue and grouped into either low copy (average <0.5) on the left, medium copy (average 0.5–10) in the middle and high copy (average >10) on the right. Black bars represent wild-type mice and white bars represent Sel P knockout mice. Number of mice used for each wild-type tissue were, 4 (brain and testes), 5 (heart) or 6 (lung) and for all 3 knockout tissues. Results represent mean +SE.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1919489&req=5

Figure 2: Comparison of Sel P knockout to wild-type mice for abundance of mRNA for selenoproteins, selenoprotein-synthesis factors and housekeeping genes. Total RNA was extracted from heart (A), lung (B), brain (C), and testes (D), which were used for cDNA synthesis and real-time PCR analysis. Levels of each target mRNA relative to hprt are shown for each tissue and grouped into either low copy (average <0.5) on the left, medium copy (average 0.5–10) in the middle and high copy (average >10) on the right. Black bars represent wild-type mice and white bars represent Sel P knockout mice. Number of mice used for each wild-type tissue were, 4 (brain and testes), 5 (heart) or 6 (lung) and for all 3 knockout tissues. Results represent mean +SE.
Mentions: Results from our comparisons are displayed in Figure 2 and reveal several interesting features regarding how genetic deletion of Sel P affects different tissues. First, both testes and brain displayed overall decreases in selenoprotein mRNA abundance as well as decreases in housekeeping mRNAs. Although statistical significance was not achieved for most of the mRNAs due to variability and low numbers of mice per group (N = 3 − 6), the brain and testes were clearly more affected than heart and lung. This was particularly evident for mRNAs for the medium and high copy genes and may reflect apoptotic or necrotic cellular damage, which may be involved in or lead to the physiological problems in these tissues. In contrast, in heart and lung mRNA abundance was decreased only in a small number of selenoproteins expressed in the low copy group. The medium and high copy selenoprotein mRNAs in heart and lung are much less affected by genetic deletion of Sel P.Figure 2.

Bottom Line: Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway.Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes.We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. peterh@pbrc.hawaii.edu

ABSTRACT
Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key role in selenium (Se) transport throughout the body. Development of a Sel P knockout mouse model has supported this notion and initial studies have indicated that selenium supply to various tissues is differentially affected by genetic deletion of Sel P. Se in the form of the amino acid, selenocysteine, is incorporated into selenoproteins at UGA codons. Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in mice affected levels of the mRNAs encoding all known members of the murine selenoprotein family, as well as three non-selenoprotein factors involved in their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2 (SBP2) and SECp43. Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes. We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

Show MeSH
Related in: MedlinePlus