Protection against reactive oxygen species by selenoproteins

Reactive oxygen species (ROS) are derived from cellular oxygen metabolism and from exogenous sources. An excess of ROS results in oxidative stress and may eventually cause cell death. ROS levels within cells and in extracellular body fluids are controlled by concerted action of enzymatic and non-enzymatic antioxidants. The essential trace element selenium exerts its antioxidant function mainly in the form of selenocysteine residues as an integral constituent of ROS-detoxifying selenoenzymes such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR) and possibly selenoprotein P (SeP). In particular, the dual role of selenoprotein P as selenium transporter and antioxidant enzyme is highlighted herein. A cytoprotective effect of selenium supplementation has been demonstrated for various cell types including neurons and astrocytes as well as endothelial cells. Maintenance of full GPx and TrxR activity by adequate dietary selenium supply has been proposed to be useful for the prevention of several cardiovascular and neurological disorders. On the other hand, selenium supplementation at supranutritional levels has been utilised for cancer prevention: antioxidant selenoenzymes as well as prooxidant effects of selenocompounds on tumor cells are thought to be involved in the anti-carcinogenic action of selenium.     

Proteomics and metabolomics of Arabidopsis responses to perturbation of glucosinolate biosynthesis

To understand plant molecular networks of glucosinolate metabolism, perturbation of aliphatic glucosinolate biosynthesis was established using inducible RNA interference (RNAi) in Arabidopsis. Two RNAi lines were chosen for examining global protein and metabolite changes using complementary proteomics and metabolomics approaches. Proteins involved in metabolism including photosynthesis and hormone metabolism, protein binding, energy, stress, and defense showed marked responses to glucosinolate perturbation. In parallel, metabolomics revealed major changes in the levels of amino acids, carbohydrates, peptides, and hormones. The metabolomics data were correlated with the proteomics results and revealed intimate molecular connections between cellular pathways/processes and glucosinolate metabolism. This study has provided an unprecedented view of the molecular networks of glucosinolate metabolism and laid a foundation towards rationale glucosinolate engineering for enhanced defense and quality.     

Metabolomics meets lipidomics: Assessing the small molecule component of metabolism

Metabolomics, including lipidomics, is emerging as a quantitative biology approach for the assessment of energy flow through metabolism and information flow through metabolic signaling; thus, providing novel insights into metabolism and its regulation, in health, healthy ageing and disease. In this forward-looking review we provide an overview on the origins of metabolomics, on its role in this postgenomic era of biochemistry and its application to investigate metabolite role and (bio)activity, from model systems to human population studies. We present the challenges inherent to this analytical science, and approaches and modes of analysis that are used to resolve, characterize and measure the infinite chemical diversity contained in the metabolome (including lipidome) of complex biological matrices. In the current outbreak of metabolic diseases such as cardiometabolic disorders, cancer and neurodegenerative diseases, metabolomics appears to be ideally situated for the investigation of disease pathophysiology from a metabolite perspective.     

Selenoproteins mediate T cell immunity through an antioxidant mechanism

Selenium is an essential dietary element with antioxidant roles in immune regulation, but there is little understanding of how this element acts at the molecular level in host defense and inflammatory disease. Selenium is incorporated into the amino acid selenocysteine (Sec), which in turn is inserted into selenoproteins in a manner dependent on Sec tRNA([Ser]Sec). To investigate the molecular mechanism that links selenium to T cell immunity, we generated mice with selenoprotein-less T cells by cell type-specific ablation of the Sec tRNA([Ser]Sec) gene (trsp). Herein, we show that these mutant mice exhibit decreased pools of mature T cells and a defect in T cell-dependent antibody responses. We also demonstrate that selenoprotein deficiency leads to oxidant hyperproduction in T cells and thereby suppresses T cell proliferation in response to T cell receptor stimulation. These findings offer novel insights into immune function of selenium and physiological antioxidants.     

Translational Redefinition of UGA Codons Is Regulated by Selenium Availability

Incorporation of selenium into ∼25 mammalian selenoproteins occurs by translational recoding whereby in-frame UGA codons are redefined to encode the selenium containing amino acid, selenocysteine (Sec). Here we applied ribosome profiling to examine the effect of dietary selenium levels on the translational mechanisms controlling selenoprotein synthesis in mouse liver. Dietary selenium levels were shown to control gene-specific selenoprotein expression primarily at the translation level by differential regulation of UGA redefinition and Sec incorporation efficiency, although effects on translation initiation and mRNA abundance were also observed. Direct evidence is presented that increasing dietary selenium causes a vast increase in ribosome density downstream of UGA-Sec codons for a subset of selenoprotein mRNAs and that the selenium-dependent effects on Sec incorporation efficiency are mediated in part by the degree of Sec-tRNA^[Ser]Sec Um34 methylation. Furthermore, we find evidence for translation in the 5′-UTRs for a subset of selenoproteins and for ribosome pausing near the UGA-Sec codon in those mRNAs encoding the selenoproteins most affected by selenium availability. These data illustrate how dietary levels of the trace element selenium can alter the readout of the genetic code to affect the expression of an entire class of proteins.     

Relationship between selenium status,selenoproteins and COVID-19 and other inflammatory diseases: A critical review

The antioxidant effects of selenium as a component of selenoproteins has been thought to modulate host immunity and viral pathogenesis. Accordingly, the association of low dietary selenium status with inflammatory and immunodeficiency has been reported in the literature; however, the causal role of selenium deficiency in chronic inflammatory diseases and viral infection is still undefined. The COVID-19, characterized by acute respiratory syndrome and caused by the novel coronavirus 2, SARS-CoV-2, has infected millions of individuals worldwide since late 2019. The severity and mortality from COVID-19 have been associated with several factor, including age, sex and selenium deficiency. However, available data on selenium status and COVID-19 are limited, and a possible causative role for selenium deficiency in COVID-19 severity has yet to be fully addressed. In this context, we review the relationship between selenium, selenoproteins, COVID-19, immune and inflammatory responses, viral infection, and aging. Regardless of the role of selenium in immune and inflammatory responses, we emphasize that selenium supplementation should be indicated after a selenium deficiency be detected, particularly, in view of the critical role played by selenoproteins in human health. In addition, the levels of selenium should be monitored after the start of supplementation and discontinued as soon as normal levels are reached. Periodic assessment of selenium levels after supplementation is a critical issue to avoid over production of toxic metabolites of selenide because under normal conditions, selenoproteins attain saturated expression levels that limits their potential deleterious metabolic effects.     

人体硒代谢与硒营养研究进展

硒是人体所必需的重要微量营养元素,综述了当前国内外人体硒代谢与硒营养的研究进展,包括硒源形式与吸收、人体的硒含量与分布、硒的代谢途径、硒的生物活化形式、硒与疾病、硒中毒和硒的安全摄入量。在此基础上,提出了针对我国硒资源分布、硒反应症分布和居民膳食结构硒摄入量的研究建议,为满足居民通过膳食和补充剂补硒预防和治疗疾病提供理论和实践指导。     

Making sense of sex and supplements: differences in the anticarcinogenic effects of selenium in men and women

The role of the essential trace mineral selenium in human health and disease is currently a subject of intense interest. In particular, the possible cancer preventive effects of dietary selenium supplementation are now being investigated in several large, randomized trials. The association between selenium status, genotoxic damage, and cancer risk remains enigmatic because epidemiologic studies have failed to consistently link low selenium status with increased cancer risk in men and women. In this paper, we considered the evidence that there are sex-based differences in the anticarcinogenic effects of selenium in humans. We focused our review on prospective human studies in which the relationship between selenium status and cancer risk in men and women was directly compared. Results from cohort studies conducted in seven countries (Belgium, China, Finland, Japan, Netherlands, Norway, and United States) were used to assess the strength of association between low selenium status and the incidence of all cancers, sex-specific cancers, and cancers at particular anatomic sites. In general, the available data support the hypothesis that cancer risk in men is more profoundly influenced by selenium status than cancer risk in women. Factors contributing to the apparent difference in the effects of selenium on cancer incidence in men and women may include sex-based differences in the metabolism and/or tissue distribution of selenium, as well as sex- or gender-related factors that influence tumor biology. Studies are needed to further define the dose-response relationship between selenium and cancer risk in men and women. A more complete understanding of the mechanisms by which selenium modulates cancer initiation and progression is needed to optimize dietary selenium supplementation as a practical cancer preventive strategy. Ultimately, achieving the ambitious goal of cancer prevention may require sex- and gender-specific approaches.     

Influence of Dietary Sodium Selenite on Tissue Selenium Levels of Growing Pigs

Twenty Norwegian Landrace pigs were divided into 5 groups and fed a basal diet consisting of a mixture of dried skim milk and whey powder together with ground barley. The diet was supplemented with 0, 0.2, 0.8, 1.2 and 2.2 μg selenium as sodium selenite and was fed for 12 weeks. The muscle selenium level was increased by a factor of about 4 and the liver selenium by a factor of about 12 when the dietary selenium supplement was increased from zero to 2.2 μg/g. There was a significant linear correlation between dietary selenium and selenium concentrations in tissues. Possible benefit for humans consuming meat from animals having received the selenium doses used in this experiment are discussed. dietary selenium; tissue levels; pigs.     

Serum Glutathione Peroxidase Activity and Blood Selenium in Pigs

Blood serum glutathione peroxidase activity and blood selenium concentration were measured in blood samples from pigs subjected to experimentally induced selenium deficiency and dietary selenium supplementation on graded levels. A highly significant correlation between blood selenium and serum GSH-Px activity in pigs, especially in selenium deficient pigs, was demonstrated. There was also a strong relationship between blood selenium concentration and serum GSH-Px activity in pigs receiving dietary selenium at graded levels. Serum GSH-Px activity exhibited an excellent close-response relationship to dietary selenium. Linear regression analysis showed that the increased serum GSH-Px activity was a function of the dietary selenium concentration. The fitness of serum in monitoring slight changes of the selenium status of pigs with help of the estimation of GSH-Px activity was discussed. The measurement of serum GSH-Px activity seems to provide a useful and rapid means for defining selenium requirements and for identifying selenium deficiency in growing pigs.     

Absorption,distribution, metabolism and excretion (ADME) of oral selenium from organic and inorganic sources: A review

BackgroundSelenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure.MethodsWe retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium.ResultsSelenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 μg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine.ConclusionSelenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.     

Selenium and selenium-antagonistic elements in nutritional cancer prevention

Selenium is an essential trace element with antioxidative, antimutagenic, antiviral and anticarcinogenic properties. There is increasing evidence that the dietary selenium intakes are sub-optimal in the populations of many countries and that human cancer mortalities would significantly decline if additional selenium was made available either through supplementation or the fortification of certain foods. An important property of selenium is its interaction with other elements that may be present in foods, the water, the workplace and the environment, e.g. As, Cu, Ni, Co, Cr, Mn, Zn, Cd, Sn, Pb, Hg, Bi, Mo, Ag, Au, etc. The sequestration of elements by selenium represents an efficient natural detoxification mechanism for some of these elements but also results in the physiological inactivation of selenium. Animal experiments confirm that the chronic exposure to low levels of these elements abolishes the cancer-protective effect of selenium. Human cancer is likewise significantly determined by the interactions of selenium with other elements, as evidenced by epidemiological, ecological and case-control studies. Cadmium, for example, is a key risk-increasing element for prostate cancer; for breast cancer, Cd, Cr, Zn are mainly contributing; for bronchial cancer (in smelter workers), Cd, As, Cr, Sb, Co, La, all these elements are in a reciprocal relationship with Se. While selenium remains the key cancer-protective trace element, the interpretation of its mode of action necessitates consideration of the effects of selenium antagonistic elements.     

The distribution of selenium and cancer mortality in the continental United States

An hypothesis was proposed that selenium concentration in the environment, as measured by the uptake of this element by forage crops, exerted an apparent effect on cancer incidence, such that cancer mortality in the continental United States was lower where the selenium concentration was high than where the concentration was low. The purpose of the present study is to test this hypothesis for statistical significance and to discover whether the apparent pattern of cancer mortality in relation to selenium distribution holds true with respect to all ages. Two main types of statistical analyses were employed: analysis of variance and trend analysis, both applied to all age groups and both sexes. Data presented in this paper show that significant interactions exist between selenium distribution and sex in relation to deaths caused by cancer of the digestive organs, respiratory organs, and the breast. Geographic variations in selenium may be viewed as variations in the intake of this element in the diet. A significant interaction may thus suggest that the particular cancer in question has in its origin a dietary factor that includes some measure of selenium intake. A discussion involving contributions from various disciplines is presented to explain the significant results reported in this paper. This paper shows that a pattern exists between the geographical distribution of selenium using forage crops as a guide for dietary intake and cancer mortality (ICD 140-209,150-159,160-163, and 174) such that an inverse relationship exists between selenium concentration in an area and cancer mortality in the same area.     

Metabolic and functional defects in selenium deficiency

This paper is concerned with present-day knowledge of the biological role of selenium, of its interaction with other nutrients including trace elements, and with the importance of selenium in human nutrition and health. Selenium has been shown to be an integral part of glutathione peroxidase, which catalyses the reduction of a large range of lipid hydroperoxides and hydrogen peroxide. The interrelation between vitamin E, selenium and polyunsaturated fatty acids is complex. First, selenium in glutathione peroxidase may control intracellular levels of hydrogen peroxide, which affect the formation of active oxygen metabolites that may serve as initiators of lipid peroxidation; this role of selenium is closely related to that of superoxide dismutases, which control intracellular levels of the superoxide anion. Secondly, vitamin E may control the formation of lipid hydroperoxides through its antioxidant function, as well as possibly entering into a structural relation with membrane phospholipids. Thirdly, glutathione peroxidase may catalyse the reduction of lipid hydroperoxides, formed from membrane lipids, to hydroxyacids without detriment to the cellular economy. In the field of human nutrition, the lack of selenium has been shown to be the cause of a cardiomyopathy known as Keshan disease, occurring in the People's Republic of China. Blood selenium levels in patients from this area are compared with blood selenium levels in three other parts of the world and the conclusion is reached that the blood selenium level of populations in Keshan disease regions are exceptionally low and that Keshan disease is the first demonstration that selenium is an essential trace element for man.     

Selenium status in Saudi Arabia

Selenium (Se) is a naturally occurring trace element that is essential for animal and human nutrition, but the range between dietary requirements and toxic levels is relatively narrow. In this review, we are interested in the beneficial effects of selenium and we report on a number of studies of the selenium status of different populations in Saudi Arabia. The Status reflects the geographical area inhabited by the populations. Apart from the few available studies reviewed here, no data on the human status of Se in Saudi Arabia has been obtained. A further objective of this paper is throw some the light on the direction of future studies.     

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500?ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6?h time course after PCT 145 plasma metabolites, 79 proteins and 7 clinical chemistry parameters were quantified. Multiple processes related to metabolism, oxidation and inflammation reacted to the PCT, as demonstrated by changes of 106 metabolites, 31 proteins and 5 clinical chemistry parameters. The PCT was applied in a dietary intervention study to evaluate if the PCT would reveal additional metabolic changes compared to non-perturbed conditions. The study consisted of a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36 overweight subjects. Of the 231 quantified parameters, 31 had different responses over time between treated and control groups, revealing differences in amino acid metabolism, oxidative stress, inflammation and endocrine metabolism. The results showed that the acute, short term metabolic responses to the PCT were different in subjects on the supplement mix compared to the controls. The PCT provided additional metabolic changes related to the dietary intervention not observed in non-perturbed conditions. Thus, a metabolomics based quantification of a standardized perturbation of metabolic homeostasis is more informative on metabolic status and subtle health effects induced by (dietary) interventions than quantification of the homeostatic situation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-011-0320-5) contains supplementary material, which is available to authorized users.     

Dietary Supplementation with Organoselenium Accelerates Recovery of Bladder Expression,but Does Not Improve Locomotor Function,following Spinal Cord Injury

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing.     

Absorption, distribution, half-life and possible routes of elimination of dietary selenium in juvenile rainbow trout (Salmo gairdneri)

1. The influence of different levels of dietary selenium on the metabolism of selenium in rainbow trout was studied using 75Se as an indicator. 2. Gastric absorption of selenium by the trout appeared to be very efficient. 3. Highest tissue concentrations of selenium were noted in the liver and kidney. 4. Blood did not concentrate selenium and the plasma was the major transport medium. 5. The liver and kidney appeared to be involved in selenium excretion based on high tissue concentrations and variations in half-lives with selenium loading. 6. The biological half-life of selenium in the tissues decreased with increased selenium loading except in the liver, which at toxic dietary selenium concentrations became longer, suggesting a rate-limiting metabolic transformation of selenium for excretion in this organ.     

空间分辨代谢组学进展和挑战

空间分辨代谢组学即整合质谱成像和代谢组学技术,对动/植物组织和细胞中内/外源性代谢物的种类、含量和差异性空间分布进行精准测定。质谱成像技术因其具有无标记、非特异、高灵敏度、高化学覆盖、元素/分子同时检测等优势,被广泛应用于动/植物组织中各类代谢物、多肽和蛋白的时空分布研究。首先介绍了代谢组学和质谱成像技术的研究现状,然后重点综述了空间分辨代谢组学在动物组织、植物组织和单细胞水平上的前沿应用。最后展望了空间分辨代谢组学技术的现有瓶颈和未来发展方向。空间分辨代谢组学是继代谢组学之后又一门新兴的分子成像组学技术,能够无标记、可视化检测动物组织中外源性药物的吸收、分布、代谢和排泄,以及植物组织中多种代谢产物的生物合成、转运途径和积累规律。该技术将推动靶向药物发现、病理机制解析和动植物生长发育密切关联的空间代谢网络调控等前沿应用研究。