Selenoprotein P—Expression, functions, and roles in mammals

Burk, Raymond F.; Hill, Kristina E.

doi:10.1016/j.bbagen.2009.03.026

Cited by 444 publications

(359 citation statements)

References 73 publications

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“…50 Thus, the liver regulates the whole-body Se distribution by sorting the metabolically available Se between the two pathways of Se-proteins synthesis and the excretory metabolite synthesis. 51 Such regulation might be passive, so that the fraction of Se that cannot be utilized for Se-proteins synthesis enters the excretory pathway. Active regulation of the excretory metabolites has been also hypothesized, 51 but not yet investigated.…”

Section: Systemic Distributionmentioning

confidence: 99%

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Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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Section: Systemic Distributionmentioning

confidence: 99%

“…51 Such regulation might be passive, so that the fraction of Se that cannot be utilized for Se-proteins synthesis enters the excretory pathway. Active regulation of the excretory metabolites has been also hypothesized, 51 but not yet investigated.…”

Section: Systemic Distributionmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

View full text Add to dashboard Cite

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“…Functional single-nucleotide polymorphisms in selenoprotein P Selenoprotein P (SePP) is the major Se transport protein in the blood (28) . Human SePP contains ten selenocysteines and accounts for approximately 65% of plasma Se.…”

Section: Functional Single-nucleotide Polymorphisms Inmentioning

confidence: 99%

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

Hesketh

Méplan

2011

Proc. Nutr. Soc.

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Micronutrients are essential for optimal human health. However, in some cases, raising intake by supplementation has not proven to be beneficial and there is even some evidence that supplementation may increase disease risk, highlighting the importance of assessing the functional status of micronutrients. Techniques such as gene microarrays and single-nucleotide polymorphism analysis have the potential to examine effects of micronutrient intake on patterns of gene expression and inter-individual variation in micronutrient metabolism. Recent genomic research related to selenium (Se) provides examples illustrating how studies of functional single-nucleotide polymorphism and gene expression patterns can reveal novel biomarkers of micronutrient function. Both in vitro and in vivo experiments show that there are functionally relevant polymorphisms in genes encoding glutathione peroxidases 1, 3 and 4, selenoprotein P, selenoprotein S and the 15 kDa selenoprotein. Disease association studies investigating these gene variants have so far been relatively small but an association of a polymorphism in the selenoprotein S gene with colorectal cancer risk has been replicated in two distinct populations. Future disease association studies should examine effects of multiple variants in combination with nutritional status. Gene microarray studies indicate that changes in Se intake alter expression of components of inflammatory, stress response and translation pathways. Our hypothesis is that Se intake and genetic factors have linked effects on stress response, inflammation and apoptotic pathways. Combining such data in a systems biology approach has the potential to identify both biomarkers of micronutrients status and sub-group populations at particular risk.

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“…69 A number of sources provide evidence of a clear connection between lipoproteins and selenium metabolism. [70][71][72][73] For example, selenoprotein P is taken up by the brain and the testes via the apolipoprotein E receptor-2, 70-72 whereas another apolipoprotein receptor, megalin, mediates its uptake by the kidney. 73 Moreover, in mouse knock-out models in which selenoprotein synthesis is compromised, both liver Apo E protein concentration, plasma cholesterol and expression of genes involved in cholesterol biosynthesis, metabolism and transport are altered, demonstrating a role for selenoproteins in the regulation of lipoprotein biosynthesis.…”

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confidence: 99%