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Dietary Selenium and Health

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

Deadline for manuscript submissions: closed (31 December 2012) | Viewed by 150924

Special Issue Editor

Director of Grants and Extramural Activities, Office of Dietary Supplements, National Institutes of Health, 6100 Executive Blvd., Room 3B01, MSC 7517, Bethesda, MD 20892-7517, USA
Interests: diet and cancer prevention; selenium; vitamin D
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Selenium is one of the most intensively studied inorganic components of the diet.  Ever since it was recognized in the 1950s that the element, which had until then been known only for its toxic effects, was also an essential nutrient, it has attracted growing interest for its role(s) in human health. Selenium exerts many of its health benefits through its incorporation into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to the production of active thyroid hormone.  More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Gaps include that the functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be improved, and effects of genotype on metabolism require further investigation.  Thus, the purpose of this special issue is to focus on the role of selenium in health and disease.

Dr. Cindy D. Davis
Guest Editor

Keywords

  • selenium
  • selenomethionine
  • selenoproteins
  • glutathione peroxidase
  • thioredoxin reductase
  • cancer
  • diabetes
  • SELECT trial

Published Papers (14 papers)

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Research

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476 KiB  
Article
Genome-Wide Association Study of Serum Selenium Concentrations
by Jian Gong, Li Hsu, Tabitha Harrison, Irena B. King, Stefan Stürup, Xiaoling Song, David Duggan, Yan Liu, Carolyn Hutter, Stephen J. Chanock, Charles B. Eaton, James R. Marshall and Ulrike Peters
Nutrients 2013, 5(5), 1706-1718; https://doi.org/10.3390/nu5051706 - 21 May 2013
Cited by 11 | Viewed by 7943
Abstract
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we [...] Read more.
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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1064 KiB  
Article
Selenium Toxicity from a Misformulated Dietary Supplement, Adverse Health Effects, and the Temporal Response in the Nail Biologic Monitor
by John Steven Morris and Stacy B. Crane
Nutrients 2013, 5(4), 1024-1057; https://doi.org/10.3390/nu5041024 - 28 Mar 2013
Cited by 85 | Viewed by 10210
Abstract
Use of dietary supplements in the U.S. has increased steadily over the last 25 years. While misformulation is uncommon, the consequences can be serious. A March 2008 voluntary market recall removed supplement products responsible for the most serious selenium toxicity outbreak that has [...] Read more.
Use of dietary supplements in the U.S. has increased steadily over the last 25 years. While misformulation is uncommon, the consequences can be serious. A March 2008 voluntary market recall removed supplement products responsible for the most serious selenium toxicity outbreak that has occurred in the U.S. We quantified selenium concentrations in the misformulated supplement products, measured the temporal response in the nail biologic monitor, and associated exposure to self-reported selenosis symptoms. Subjects recruited through state health departments and referrals provided samples of the misformulated supplement products, exposure information, monthly toenail and or fingernail clippings or onycholysitic nail fragments, and listed their newly onset adverse health effects attributed to selenium toxicity. Ninety-seven subjects enrolled and submitted at least one test sample. Peak selenium concentrations (up to 18.3 and 44.1 μg/g for toenails and fingernails, respectively) were measured. Multiple samples (52 total) of all six recalled supplement lots were analyzed ranging from 22,300 to 32,200 μg selenium per daily dose. Average consumption was 30.9 ± 13.9 doses; 73 subjects provided follow-up data on selenosis symptoms at 2.50 ± 0.14 years. Nail samples accurately reflect exposure in this selenium toxicity outbreak, which resulted in long-term/permanent adverse health effects. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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572 KiB  
Article
Selenium for the Prevention of Cutaneous Melanoma
by Pamela B. Cassidy, Heidi D. Fain, James P. Cassidy, Jr., Sally M. Tran, Philip J. Moos, Kenneth M. Boucher, Russell Gerads, Scott R. Florell, Douglas Grossman and Sancy A. Leachman
Nutrients 2013, 5(3), 725-749; https://doi.org/10.3390/nu5030725 - 07 Mar 2013
Cited by 39 | Viewed by 8495
Abstract
The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to [...] Read more.
The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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436 KiB  
Article
Daily Dietary Selenium Intake in a High Selenium Area of Enshi, China
by Yang Huang, Quanxin Wang, Jin Gao, Zhiqing Lin, Gary S. Bañuelos, Linxi Yuan and Xuebin Yin
Nutrients 2013, 5(3), 700-710; https://doi.org/10.3390/nu5030700 - 05 Mar 2013
Cited by 87 | Viewed by 9284
Abstract
Enshi is a high selenium (Se) region in Hubei, China, where human selenosis was observed between 1958 and 1963. This study investigated the daily dietary Se intake of residents in Shadi, a town located 72 km northeast of Enshi City, to assess the [...] Read more.
Enshi is a high selenium (Se) region in Hubei, China, where human selenosis was observed between 1958 and 1963. This study investigated the daily dietary Se intake of residents in Shadi, a town located 72 km northeast of Enshi City, to assess the risk of human selenosis in the high Se area. Foods consumed typically by the local residents and their hair samples were analyzed for total Se concentration. Concentrations of Se in different diet categories were as follows: cereals: 0.96 ± 0.90 mg kg−1 DW in rice and 0.43 ± 0.55 mg kg−1 DW in corn; tuber: 0.28 ± 0.56 mg kg−1 in potato and 0.36 ± 0.12 mg kg−1 in sweet potato; vegetables: ranging from 0.23 ± 1.00 mg kg−1 in carrot to 1.57 ± 1.06 mg kg−1 in kidney bean; animal proteins: 1.99 ± 1.11 mg kg−1 in chicken and egg. Based on the food Se concentrations and the daily per-capita consumption, the estimated daily Se intake in Shadi was 550 ± 307 µg per capita. Moreover, the Se concentrations in the hairs of local adult residents were 3.13 ± 1.91 mg kg−1 (n = 122) and 2.21 ± 1.14 mg kg−1 (n = 122) for females and males, respectively, suggesting that females might be exposed to higher levels of Se from daily cooking. Although there was no human selenosis occurrence in recent years, the high level of the daily Se intake suggested that the potential risk of selenosis for local residents, especially females, might be a matter of concern. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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543 KiB  
Article
Selenoprotein-Transgenic Chlamydomonas reinhardtii
by Qintang Hou, Shi Qiu, Qiong Liu, Jing Tian, Zhangli Hu and Jiazuan Ni
Nutrients 2013, 5(3), 624-636; https://doi.org/10.3390/nu5030624 - 26 Feb 2013
Cited by 25 | Viewed by 7718
Abstract
Selenium (Se) deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with [...] Read more.
Selenium (Se) deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with the application of a newly developed system, is thus very important for studying the mechanism of Se in nutrition. The use of Chlamydomonas reinhardtii (C. reinhardtii) as a biological vector to express an heterogeneous protein is still at the initial stages of development. In order to investigate the possibility of using this system to express selenoproteins, human 15-KDa selenoprotein (Sep15), a small but widely distributed selenoprotein in mammals, was chosen for the expression platform test. Apart from the wild-type human Sep15 gene fragment, two Sep15 recombinants were constructed containing Sep15 open reading frame (ORF) and the selenocysteine insertion sequence (SECIS) element from either human Sep15 or C. reinhardtii selenoprotein W1, a highly expressed selenoprotein in this alga. Those Sep15-containing plasmids were transformed into C. reinhardtii CC-849 cells. Results showed that Sep15 fragments were successfully inserted into the nuclear genome and expressed Sep15 protein in the cells. The transgenic and wild-type algae demonstrated similar growth curves in low Se culture medium. To our knowledge, this is the first report on expressing human selenoprotein in green alga. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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645 KiB  
Article
Prostatic Response to Supranutritional Selenium Supplementation: Comparison of the Target Tissue Potency of Selenomethionine vs. Selenium-Yeast on Markers of Prostatic Homeostasis
by David J. Waters, Shuren Shen, Seema S. Kengeri, Emily C. Chiang, Gerald F. Combs, Jr., J. Steven Morris and David G. Bostwick
Nutrients 2012, 4(11), 1650-1663; https://doi.org/10.3390/nu4111650 - 06 Nov 2012
Cited by 17 | Viewed by 8901
Abstract
Prostate cancer is the product of dysregulated homeostasis within the aging prostate. Supplementation with selenium in the form of selenized yeast (Se-yeast) significantly reduced prostate cancer incidence in the Nutritional Prevention of Cancer Trial. Conversely, the Selenium and Vitamin E Cancer Prevention Trial [...] Read more.
Prostate cancer is the product of dysregulated homeostasis within the aging prostate. Supplementation with selenium in the form of selenized yeast (Se-yeast) significantly reduced prostate cancer incidence in the Nutritional Prevention of Cancer Trial. Conversely, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no such cancer-protective advantage using selenomethionine (SeMet). The possibility that SeMet and Se-yeast are not equipotent in promoting homeostasis and cancer risk reduction in the aging prostate has not been adequately investigated; no direct comparison has ever been reported in man or animals. Here, we analyzed data on prostatic responses to SeMet or Se-yeast from a controlled feeding trial of 49 elderly beagle dogs—the only non-human species to frequently develop prostate cancer during aging—randomized to one of five groups: control; low-dose SeMet, low-dose Se-yeast (3 μg/kg); high-dose SeMet, high-dose Se-yeast (6 μg/kg). After seven months of supplementation, we found no significant selenium form-dependent differences in toenail or intraprostatic selenium concentration. Next, we determined whether SeMet or Se-yeast acts with different potency on six markers of prostatic homeostasis that likely contribute to prostate cancer risk reduction—intraprostatic dihydrotestosterone (DHT), testosterone (T), DHT:T, and epithelial cell DNA damage, proliferation, and apoptosis. By analyzing dogs supplemented with SeMet or Se-yeast that achieved equivalent intraprostatic selenium concentration after supplementation, we showed no significant differences in potency of either selenium form on any of the six parameters over three different ranges of target tissue selenium concentration. Our findings, which represent the first direct comparison of SeMet and Se-yeast on a suite of readouts in the aging prostate that reflect flux through multiple gene networks, do not further support the notion that the null results of SELECT are attributable to differences in prostatic consequences achievable through daily supplementation with SeMet, rather than Se-yeast. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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Review

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203 KiB  
Review
The Relationship between Selenoprotein P and Glucose Metabolism in Experimental Studies
by Jinyuan Mao and Weiping Teng
Nutrients 2013, 5(6), 1937-1948; https://doi.org/10.3390/nu5061937 - 29 May 2013
Cited by 48 | Viewed by 11612
Abstract
Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although [...] Read more.
Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although they cannot distinguish between cause and effect. Selenoprotein P (Sepp1) is central to selenium homeostasis and widely expressed in the organism. Here we review the interaction between Sepp1 and glucose metabolism with an emphasis on experimental evidence. In models with or without gene modification, glucose and insulin can regulate Sepp1 expression in the pancreas and liver, and vice versa. Especially in the liver, Sepp1 is regulated virtually like a gluconeogenic enzyme. Combining these data suggests that there could be a feedback regulation between hepatic Sepp1 and pancreatic insulin and that increasing circulating Sepp1 might be the result rather than the cause of abnormal glucose metabolism. Future studies specifically designed to overexpress Sepp1 are needed in order to provide a more robust link between Sepp1 and type 2 diabetes. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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980 KiB  
Review
Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems
by Claire M. Weekley, Jade B. Aitken, Lydia Finney, Stefan Vogt, Paul K. Witting and Hugh H. Harris
Nutrients 2013, 5(5), 1734-1756; https://doi.org/10.3390/nu5051734 - 21 May 2013
Cited by 60 | Viewed by 12142
Abstract
Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in [...] Read more.
Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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550 KiB  
Review
Selenium Supranutrition: Are the Potential Benefits of Chemoprevention Outweighed by the Promotion of Diabetes and Insulin Resistance?
by Caroline R. B. Rocourt and Wen-Hsing Cheng
Nutrients 2013, 5(4), 1349-1365; https://doi.org/10.3390/nu5041349 - 19 Apr 2013
Cited by 72 | Viewed by 13451
Abstract
Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium [...] Read more.
Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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426 KiB  
Review
Is Selenium a Potential Treatment for Cancer Metastasis?
by Yu-Chi Chen, K. Sandeep Prabhu and Andrea M. Mastro
Nutrients 2013, 5(4), 1149-1168; https://doi.org/10.3390/nu5041149 - 08 Apr 2013
Cited by 112 | Viewed by 14749
Abstract
Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se [...] Read more.
Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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999 KiB  
Review
Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)
by Holly L. Nicastro and Barbara K. Dunn
Nutrients 2013, 5(4), 1122-1148; https://doi.org/10.3390/nu5041122 - 03 Apr 2013
Cited by 62 | Viewed by 14613
Abstract
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that [...] Read more.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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363 KiB  
Review
Is There a Therapeutic Role for Selenium in Alpha-1 Antitrypsin Deficiency?
by Catherine M. Greene, Roohi Chhabra and Noel G. McElvaney
Nutrients 2013, 5(3), 758-770; https://doi.org/10.3390/nu5030758 - 11 Mar 2013
Cited by 4 | Viewed by 8096
Abstract
Selenium is an essential trace mineral of fundamental importance to human health. Much of its beneficial influence is attributed to its presence within selenoproteins, a group of proteins containing the rare amino acid selenocysteine. There are 25 known human selenoproteins including glutathione peroxidases, [...] Read more.
Selenium is an essential trace mineral of fundamental importance to human health. Much of its beneficial influence is attributed to its presence within selenoproteins, a group of proteins containing the rare amino acid selenocysteine. There are 25 known human selenoproteins including glutathione peroxidases, thioredoxin reductases and selenoproteins. Selenoprotein S (SEPS1) is an endoplasmic reticulum (ER) resident selenoprotein involved in the removal of misfolded proteins from the ER. SEPS1 expression can be induced by ER stress, an event that is associated with conformational disorders and occurs due to accumulation of misfolded proteins within the ER. Alpha-1 antitrypsin (AAT) deficiency, also known as genetic emphysema, is a conformational disorder in which the roles of ER stress, SEPS1 and selenium have been investigated. SEPS1 can relieve ER stress in an in vitro model of AAT deficiency by reducing levels of active ATF6 and inhibiting grp78 promoter- and NFκB activity; some of these effects are enhanced in the presence of selenium supplementation. Other studies examining the molecular mechanisms by which selenium mediates its anti-inflammatory effects have identified a role for prostaglandin 15d-PGJ2 in targeting NFκB and PPARγ. Together these ER stress-relieving and anti-inflammatory properties suggest a therapeutic potential for selenium supplementation in genetic emphysema. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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349 KiB  
Review
Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype
by Jacob Joseph and Joseph Loscalzo
Nutrients 2013, 5(2), 340-358; https://doi.org/10.3390/nu5020340 - 31 Jan 2013
Cited by 50 | Viewed by 9278
Abstract
Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of [...] Read more.
Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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477 KiB  
Review
Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation
by Huawei Zeng, Jay J. Cao and Gerald F. Combs, Jr.
Nutrients 2013, 5(1), 97-110; https://doi.org/10.3390/nu5010097 - 10 Jan 2013
Cited by 125 | Viewed by 13599
Abstract
Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell [...] Read more.
Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health. Full article
(This article belongs to the Special Issue Dietary Selenium and Health)
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