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The Role of Selenium in Health and Disease

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 83569

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Special Issue Editors

Dr. Catherine Méplan

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Guest Editor

School of Biomedical Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK
Interests: selenium; nutritional genomics; selenoproteins; single nucleotide polymorphisms; cancer; cancer biomarkers; micronutrients; proteomics; transcriptomics; colorectal function

Dr. David J. Hughes

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Guest Editor

Cancer Biology and Therapeutics Group, UCD Conway Institute, University College Dublin, Dublin 4, Ireland
Interests: nutritional epidemiology of cancer; genetic epidemiology of cancer; cancer biomarkers; micronutrients; selenium; single nucleotide polymorphisms; genomics; microbiome; gut barrier function

Special Issue Information

Dear Colleagues,

We invite you to contribute to a Special Issue of Nutrients, entitled “Role of Selenium in Health and Disease”.

Recent advances in our understanding of the relationship between the essential micronutrient selenium and human health and disease showed that selenium and selenoproteins are central to metabolic pathways commonly affected in most complex disorders. As a constituent of selenoproteins, selenium plays a key role in the response to oxidative or endoplasmic reticulum stress, inflammatory and immune signalling, redox control and mitochondrial function. Thus, not surprisingly, selenium and selenoproteins have been linked to complex disorders, such as cancer, cardiovascular disease, diabetes, reproductive health, Alzheimer's disease, and viral infections, among others.

With the ‘omics revolution’, functional polymorphisms in selenoprotein genes and gene x nutrient interactions were found to modify the risk for many cancers and other complex disorders. Furthermore high-throughput molecular profiling ‘technologies’ revealed the impact of changes in selenium status on gene and protein expression in molecular pathways involved in disease development and progression.

Inter-individual variability in selenium status has been shown to be affected by age, sex, and lifestyle factors such as alcohol consumption. As these factors are known contributors to the etiopathogenesis of most complex age-related disorders, further investigation is needed to clarify the relevance of selenium intake values together with genomic aspects of selenium biology. This knowledge has the potential to provide invaluable insight for future understanding, prevention and treatment of many chronic diseases.

In this Special Issue, we welcome the submission of either original research manuscripts or reviews of the scientific literature. Manuscripts across a broad range of topics will be considered, but priority will be given to manuscripts that address the following topics:

Selenium and complex disorders (e.g., cancer, type 2 diabetes, Alzheimer’s disease, autoimmune disorders, etc.)
Genomics and Selenium/selenoproteins
Selenium/selenoproteins and ageing (e.g., healthy ageing, longevity, age-related disorders)
Selenium/selenoproteins and cognitive function
Selenium/selenoproteins and infectious diseases/viruses
Selenium/selenoproteins and stress response mechanisms (e.g., inflammatory signalling, immune function, ER stress)
Human evolution of selenium biology
Selenium/selenoproteins as clinical biomarkers of disease and health status
Biomedical/therapeutic application of Se supplementations and Se-containing drugs

Dr. Catherine Méplan
Dr. David J. Hughes
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

Selenium
Selenoproteins
Cancer
Type 2 diabetes
Ageing
Cognitive function
Biomarker
Genomics
Inflammation
Immune function

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

4 pages, 215 KiB

Open AccessEditorial

The Role of Selenium in Health and Disease: Emerging and Recurring Trends

by Catherine Méplan and David J. Hughes

Nutrients 2020, 12(4), 1049; https://doi.org/10.3390/nu12041049 - 10 Apr 2020

Cited by 22 | Viewed by 5315

Abstract

In this Special Issue of Nutrients, “The Role of Selenium in Health and Disease” covers diverse diseases in the 8 original research articles and 2 reviews, such as cardiovascular disorders (CVD), metabolic syndrome, obesity, cancer, and viral infection, and highlights novel potential [...] Read more.

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

Research

Jump to: Editorial, Review

12 pages, 2186 KiB

Open AccessArticle

Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery

by Ellen C. D. Kühn-Heid, Eike C. Kühn, Julia Ney, Sebastian Wendt, Julian Seelig, Christian Schwiebert, Waldemar B. Minich, Christian Stoppe and Lutz Schomburg

Nutrients 2019, 11(9), 2005; https://doi.org/10.3390/nu11092005 - 25 Aug 2019

Cited by 12 | Viewed by 4043

Abstract

Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, “endpoint 1”; OR 29.9, CI 3.3–268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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11 pages, 1122 KiB

Open AccessArticle

Selenoprotein-P Deficiency Predicts Cardiovascular Disease and Death

by Lutz Schomburg, Marju Orho-Melander, Joachim Struck, Andreas Bergmann and Olle Melander

Nutrients 2019, 11(8), 1852; https://doi.org/10.3390/nu11081852 - 9 Aug 2019

Cited by 80 | Viewed by 6099

Abstract

Selenoprotein-P (SELENOP) is the main carrier of selenium to target organs and reduces tissue oxidative stress both directly and by delivering selenium to protective selenoproteins. We tested if the plasma concentration of SELENOP predicts cardiovascular morbidity and mortality in the primary preventive setting. SELENOP was measured from the baseline exam in 2002–2006 of the Malmö Preventive Project, a population-based prospective cohort study, using a validated ELISA. Quintiles of SELENOP concentration were related to the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event in 4366 subjects during a median (interquartile range) follow-up time of 9.3 (8.3–11) years using Cox proportional Hazards Model adjusting for cardiovascular risk factors. Compared to subjects in the lowest quintile of SELENOP, the risk of all three endpoints was significantly lower in quintiles 2–5. The risk (multivariate adjusted hazard ratio, 95% CI) decreased gradually with the lowest risk in quintile 4 for all-cause mortality (0.57, 0.48–0.69) (p < 0.001), cardiovascular mortality (0.52, 0.37–0.72) (p < 0.001), and first cardiovascular event (0.56, 0.44–0.71) (p < 0.001). The lower risk of a first cardiovascular event in quintiles 2–5 as compared to quintile 1 was significant for both coronary artery disease and stroke. We conclude that the 20% with lowest SELENOP concentrations in a North European population without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality, and preventive selenium supplementation studies stratified for these subjects are warranted. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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15 pages, 4583 KiB

Open AccessArticle

Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

by Daniel J. Torres, Matthew W. Pitts, Ann C. Hashimoto and Marla J. Berry

Nutrients 2019, 11(7), 1693; https://doi.org/10.3390/nu11071693 - 23 Jul 2019

Cited by 10 | Viewed by 5663

Abstract

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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13 pages, 3275 KiB

Open AccessFeature PaperArticle

Selenized Plant Oil Is an Efficient Source of Selenium for Selenoprotein Biosynthesis in Human Cell Lines

by Jordan Sonet, Maurine Mosca, Katarzyna Bierla, Karolina Modzelewska, Anna Flis-Borsuk, Piotr Suchocki, Iza Ksiazek, Elzbieta Anuszewska, Anne-Laure Bulteau, Joanna Szpunar, Ryszard Lobinski and Laurent Chavatte

Nutrients 2019, 11(7), 1524; https://doi.org/10.3390/nu11071524 - 4 Jul 2019

Cited by 8 | Viewed by 4443

Abstract

Selenium is an essential trace element which is incorporated in the form of a rare amino acid, the selenocysteine, into an important group of proteins, the selenoproteins. Among the twenty-five selenoprotein genes identified to date, several have important cellular functions in antioxidant defense, cell signaling and redox homeostasis. Many selenoproteins are regulated by the availability of selenium which mostly occurs in the form of water-soluble molecules, either organic (selenomethionine, selenocysteine, and selenoproteins) or inorganic (selenate or selenite). Recently, a mixture of selenitriglycerides, obtained by the reaction of selenite with sunflower oil at high temperature, referred to as Selol, was proposed as a novel non-toxic, highly bioavailable and active antioxidant and antineoplastic agent. Free selenite is not present in the final product since the two phases (water soluble and oil) are separated and the residual water-soluble selenite discarded. Here we compare the assimilation of selenium as Selol, selenite and selenate by various cancerous (LNCaP) or immortalized (HEK293 and PNT1A) cell lines. An approach combining analytical chemistry, molecular biology and biochemistry demonstrated that selenium from Selol was efficiently incorporated in selenoproteins in human cell lines, and thus produced the first ever evidence of the bioavailability of selenium from selenized lipids. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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13 pages, 938 KiB

Open AccessCommunication

Selenium and Health: An Update on the Situation in the Middle East and North Africa

by Sohayla A. Z. Ibrahim, Abdelhamid Kerkadi and Abdelali Agouni

Nutrients 2019, 11(7), 1457; https://doi.org/10.3390/nu11071457 - 27 Jun 2019

Cited by 48 | Viewed by 6354

Abstract

Selenium (Se) is an important trace element that should be present in the diet of all age groups to provide an adequate intake. Se is incorporated in 25 known selenoproteins, which mediate the biological effects of Se including, immune response regulation, maintenance of thyroid function, antioxidant defense, and anti-inflammatory actions. A balanced intake of Se is critical to achieve health benefits because depending on its status, Se has been found to play physiological roles or contribute to the pathophysiology of various diseases including, neurodegenerative diseases, diabetes, cancer, and cardiovascular disorders. Se status and intake are very important to be known for a specific population as the levels of Se are highly variable among different populations and regions. In the Middle East and North African (MENA) region, very little is known about the status of Se. Studies available show that Se status is widely variable with some countries being deficient, some over sufficient, and some sufficient. This variability was apparent even within the same country between regions. In this review, we summarized the key roles of Se in health and disease and discussed the available data on Se status and intake among countries of the MENA region. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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19 pages, 317 KiB

Open AccessFeature PaperArticle

Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

by Veronika Fedirko, Mazda Jenab, Catherine Méplan, Jeb S. Jones, Wanzhe Zhu, Lutz Schomburg, Afshan Siddiq, Sandra Hybsier, Kim Overvad, Anne Tjønneland, Hanane Omichessan, Vittorio Perduca, Marie-Christine Boutron-Ruault, Tilman Kühn, Verena Katzke, Krasimira Aleksandrova, Antonia Trichopoulou, Anna Karakatsani, Anastasia Kotanidou, Rosario Tumino, Salvatore Panico, Giovanna Masala, Claudia Agnoli, Alessio Naccarati, Bas Bueno-de-Mesquita, Roel C.H. Vermeulen, Elisabete Weiderpass, Guri Skeie, Therese Haugdahl Nøst, Leila Lujan-Barroso, J. Ramón Quirós, José María Huerta, Miguel Rodríguez-Barranco, Aurelio Barricarte, Björn Gylling, Sophia Harlid, Kathryn E. Bradbury, Nick Wareham, Kay-Tee Khaw, Marc Gunter, Neil Murphy, Heinz Freisling, Kostas Tsilidis, Dagfinn Aune, Elio Riboli, John E. Hesketh and David J. Hughes Show full author list Hide full author list

Nutrients 2019, 11(4), 935; https://doi.org/10.3390/nu11040935 - 25 Apr 2019

Cited by 24 | Viewed by 8310

Abstract

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (P_ACT = 0.10; P_ACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

12 pages, 624 KiB

Open AccessArticle

Gender Differences with Dose–Response Relationship between Serum Selenium Levels and Metabolic Syndrome—A Case-Control Study

by Chia-Wen Lu, Hao-Hsiang Chang, Kuen-Cheh Yang, Chien-Hsieh Chiang, Chien-An Yao and Kuo-Chin Huang

Nutrients 2019, 11(2), 477; https://doi.org/10.3390/nu11020477 - 24 Feb 2019

Cited by 29 | Viewed by 4869

Abstract

Few studies have investigated the association between selenium and metabolic syndrome. This study aimed to explore the associations between the serum selenium level and metabolic syndrome as well as examining each metabolic factor. In this case-control study, the participants were 1165 adults aged ≥40 (65.8 ± 10.0) years. Serum selenium was measured by inductively coupled plasma-mass spectrometry. The associations between serum selenium and metabolic syndrome were examined by multivariate logistic regression analyses. The least square means were computed by general linear models to compare the serum selenium levels in relation to the number of metabolic factors. The mean serum selenium concentration was 96.34 ± 25.90 μg/L, and it was positively correlated with waist circumference, systolic blood pressure, triglycerides, fasting glucose, and homeostatic model assessment insulin resistance (HOMA-IR) in women, but it was only correlated with fasting glucose and HOMA-IR in men. After adjustment, the odds ratios (ORs) of having metabolic syndrome increased with the selenium quartile groups (p for trend: <0.05), especially in women. The study demonstrated that the serum selenium levels were positively associated with metabolic syndrome following a non-linear dose–response trend. Selenium concentration was positively associated with insulin resistance in men and women, but it was associated with adiposity and lipid metabolism in women. The mechanism behind this warrants further confirmation. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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12 pages, 492 KiB

Open AccessArticle

Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer

by David J. Hughes, Tereza Kunická, Lutz Schomburg, Václav Liška, Niall Swan and Pavel Souček

Nutrients 2018, 10(11), 1812; https://doi.org/10.3390/nu10111812 - 21 Nov 2018

Cited by 39 | Viewed by 6404

Abstract

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. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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Review

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33 pages, 4704 KiB

Open AccessReview

Selenium, Selenoproteins and Viral Infection

by Olivia M. Guillin, Caroline Vindry, Théophile Ohlmann and Laurent Chavatte

Nutrients 2019, 11(9), 2101; https://doi.org/10.3390/nu11092101 - 4 Sep 2019

Cited by 329 | Viewed by 24785

Abstract

Reactive oxygen species (ROS) are frequently produced during viral infections. Generation of these ROS can be both beneficial and detrimental for many cellular functions. When overwhelming the antioxidant defense system, the excess of ROS induces oxidative stress. Viral infections lead to diseases characterized by a broad spectrum of clinical symptoms, with oxidative stress being one of their hallmarks. In many cases, ROS can, in turn, enhance viral replication leading to an amplification loop. Another important parameter for viral replication and pathogenicity is the nutritional status of the host. Viral infection simultaneously increases the demand for micronutrients and causes their loss, which leads to a deficiency that can be compensated by micronutrient supplementation. Among the nutrients implicated in viral infection, selenium (Se) has an important role in antioxidant defense, redox signaling and redox homeostasis. Most of biological activities of selenium is performed through its incorporation as a rare amino acid selenocysteine in the essential family of selenoproteins. Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses. In addition, several selenoprotein members, including glutathione peroxidases (GPX), thioredoxin reductases (TXNRD) seemed important in different models of viral replication. Finally, the formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenoproteins in viral cycle. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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10 pages, 495 KiB

Open AccessReview

Role of Selenoprotein F in Protein Folding and Secretion: Potential Involvement in Human Disease

by Bingyu Ren, Min Liu, Jiazuan Ni and Jing Tian

Nutrients 2018, 10(11), 1619; https://doi.org/10.3390/nu10111619 - 2 Nov 2018

Cited by 40 | Viewed by 5813

Abstract

Selenoproteins form a group of proteins of which its members contain at least one selenocysteine, and most of them serve oxidoreductase functions. Selenoprotein F (SELENOF), one of the 25 currently identified selenoproteins, is located in the endoplasmic reticulum (ER) organelle and is abundantly expressed in many tissues. It is regulated according to its selenium status, as well as by cell stress conditions. SELENOF may be functionally linked to protein folding and the secretion process in the ER. Several studies have reported positive associations between SELENOF genetic variations and several types of cancer. Also, altered expression levels of SELENOF have been found in cancer cases and neurodegenerative diseases. In this review, we summarize the current understanding of the structure, expression, and potential function of SELENOF and discuss its possible relation with various pathological processes. Full article

(This article belongs to the Special Issue The Role of Selenium in Health and Disease)

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