Essential Trace Element Selenium Research Articles

Selenium Supplementation and Cancer Prevention

The essential trace element selenium has been shown to have cancer preventive potential by a converging body of epidemiologic and preclinical studies. Although randomized controlled trials suggest a benefit against liver cancer, results at other sites are not as consistent. The Nutritional Prevention of Cancer Trial provided evidence that selenium-enriched yeast can protect against total cancer incidence and the incidence of prostate, lung, and colorectal cancer. In contrast, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenomethionine provided no protection against prostate, lung, or colorectal cancer. Results from these trials suggest that the cancer protective effects of selenium probably depend on the baseline selenium status of the individual, chemical form of selenium utilized, gender, and genetic polymorphisms in selenoproteins or in cancer-related processes.

Multiple forms of selenoprotein P in a candidate human plasma standard reference material

Selenoprotein P (SePP) is a unique selenium-containing protein responsible for the transport and distribution of the essential trace element selenium (Se) through the human body with the concentration of SePP in human blood representing the most useful marker of Se nutritional status. Although SePP has been extensively studied, the structure of SePP in human plasma remains unresolved. Two potential isoforms of SePP have been identified by Western blot analyses distinguished principally by differences in migration (51 kDa and 61 kDa). The biological relevance of the smaller isoform has been called into question by several studies reporting only one major SePP form (69 kDa) suggesting that the shorter 51 kDa is an artifact of protease activity during the SePP purification process. A deficiency of these Western blot analyses is that no information can be gleaned regarding the Se content of the potential isoforms. This study reports a characterization of SePP isoforms in a human plasma Standard Reference Material representative of a healthy US population. Following immunoprecipitation, three SePP isoforms were unequivocally identified at 45 kDa, 49 kDa and 57 kDa (termed as SePP45, SePP49 and SePP57) by LC-MS/MS analyses from a spectral searching approach. Selenium (Se) was detected by gel electrophoresis LA-ICP-MS in SePP49 and SePP57 which was confirmed by the identification of three selenopeptides covering the SePP sequence from residues 312-346 by LC-MS/MS analyses utilizing a sequence searching approach. Conversely, neither Se nor peptides covering SePP sequence from residues 306-346 was identified in SePP45 which suggests that SePP45 is a truncated isoform transcriptionally terminated at the 2nd in-frame UGA codon thereby terminating the protein with the Ser residue at position 299. An additional band at 23 kDa was found to contain Se but no peptides of SePP. Instead, glutathione peroxidase 3 (GPx3) was unequivocally identified within the band presumably being co-immunoprecipitated with the SePP providing preliminary evidence that SePP and GPx3 interaction may take place in vivo.

The PACAP-Regulated Gene Selenoprotein T Is Highly Induced in Nervous, Endocrine, and Metabolic Tissues during Ontogenetic and Regenerative Processes

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.

Selenium and Alzheimer's Disease: A Systematic Review

Preventing Alzheimer's disease (AD) would require knowledge about its etiology to a degree of detail not yet available. The major hurdle in understanding the disease lies in teasing out the various causes and their complex interactions. Since considerable data have accrued showing that the essential trace element selenium (Se) might play different roles in the progression of AD, we conducted a systematic review of the literature regarding Se and AD. We identified 9 placebo-controlled studies (6 were multiple supplement trials including Se, 1 was ongoing), 4 prospective, 4 cross-sectional, 15 case control, 24 autopsy studies, as well studies in animals and cells. There is an absence of consistent clinical evidence as to whether supplementation of Se is beneficial in the treatment of AD and how Se levels are altered in brain, cerebrospinal fluid, and blood of patients with AD. Some longitudinal and cross-sectional studies, however, show an association of Se status and cognitive function. Findings from molecular biology reveal a decisive role of Se in the pathogenesis of AD. In summary, the current state of knowledge provides no evidence for a role of Se in the treatment of AD, but allows speculation on a potential preventive relevance. Large trials of long-term duration could provide definitive answers.

A COMPARATIVE STUDY OF HEPATIC TRACE ELEMENT LEVELS IN WILD MOOSE, ROE DEER, AND REINDEER FROM NORWAY

Liver samples from 422 wild moose (Alces alces), 280 roe deer (Capreolus capreolus), and 73 reindeer (Rangifer tarandus) collected by hunters in various localities in Norway, 2002-2003, were analyzed for the essential trace elements cobalt, copper (Cu), manganese (Mn), molybdenum, selenium (Se), and zinc. Significant differences in hepatic concentrations among species were found for all elements except for Mn, and considerable individual and geographic variations were seen. Roe deer had statistically significant lower Se levels (median: 0.51 μg Se/g dry weight) than did moose (0.77 μg Se/g) and reindeer (0.85 μg Se/g). Moose from two coastal municipalities with high precipitation had considerably higher Se concentrations than those from the other localities studied. Seventy-nine roe deer (28%) and 36 moose (9%) had Se concentrations below that regarded as deficient in domestic ruminants. The Se status in roe deer was lower than previously reported in Europe. Moose had a significantly higher Cu (222 μg Cu/g dw) than did roe deer (112 μg Cu/g) and reindeer (105 μg Cu/g). The Cu status of moose and roe deer in Norway are among the highest reported in Europe. However, a suboptimal Se and Cu status was found in moose from Tvedestrand, a population which has suffered from a reduced condition and productivity. The variability in trace element status among hunted cervids, with no apparent signs of deficiency or toxicity, probably reflects adaptations in these wild ruminant species to cope with this. However, subtle clinical signs and lesions are difficult to detect and further research is needed.

Redox Pioneer: Professor Leopold Flohé

Leopold Flohé is recognized here as a Redox Pioneer because has published a article on antioxidant/redox biology, as first author, that has been cited more than 1,000 times, and more than 20 articles have been cited more than 100 times. He obtained the medical doctorate at the Institute of Pharmacology and Toxicology at the University of Tübingen, Germany, in 1968. He held positions in both Academia (Tübingen, Aachen, and Braunschweig, Germany) and industry (Aachen). He is now operating the biotech company MOLISA in Magdeburg, Germany, while teaching as guest professor at the local university. Dr. Flohé is the pioneer who established the selenoprotein nature of glutathione peroxidase (GPx), the first and, for almost 10 years, the only selenoprotein known in animals. His work was pivotal to link the essential trace element selenium to metabolic processes, which led the Food and Drug Administration (FDA) to approve selenium supplementation for humans in 1980, and stimulated selenium biochemistry in general. In recent years, he embarked on investigating how pathogens protect themselves from oxidative killing. His inseminating studies on the thiol-dependent hydroperoxide metabolism of trypanosomatids and mycobacteria defined molecular drug targets, paving the way to new therapeutic strategies for neglected diseases affecting the people of developing countries.

Selenium and the Thyroid: A Close-Knit Connection

The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease. Clinical reports as well as a large number of biochemical articles linking selenium to thyroid have been considered. Interventional, prospective, randomized, controlled studies, including large observational studies, supplementing selenium in autoimmune thyroid disease, together with review articles published in Medline and Pubmed have undergone scrutiny. The methodological differences and variety of results emerging from these trials have been analyzed. Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination. However, considerable discord remains as to who should comprise target groups for selenium treatment, who will most benefit from such treatment, the precise impact of the basal antithyroid peroxidase level, and the effect of disease duration on the treatment outcome. Clearly, further in-depth studies and evaluation are required concerning the mechanism of action of selenium as well as the choice of supplements or dietary intake. Maintenance of "selenostasis" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease.

Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium

Simultaneous exposure of lab animals to toxic doses of the human carcinogen arsenic (As) and the essential trace element selenium (Se) results in a remarkable mutual detoxification. A likely basis for this is the in vivo formation and biliary excretion of seleno-bis(S-glutathionyl) arsinium ion [(GS)(2)AsSe](-); however, the transport protein responsible for the biliary efflux of [(GS)(2)AsSe](-) has not been identified. The multidrug resistance protein 2 (MRP2/ABCC2) is an adenosine triphosphate (ATP)-binding cassette transporter expressed at the canalicular membrane of hepatocytes. Rat Mrp2 is known to excrete the As glutathione (GSH/GS-) conjugates arsenic triglutathione [As(GS)(3)] and monomethyl arsenic diglutathione [CH(3)As(GS)(2)] into bile, and in vitro studies have established As(GS)(3) as a substrate for human MRP2. In the present study, membrane vesicles prepared from human embryonic kidney (HEK293T) cells transfected with human MRP2 were used to demonstrate that MRP2 transports [(GS)(2)AsSe](-). In addition, the characteristics of MRP2 transport of As(GS)(3) and [(GS)(2)AsSe](-) were investigated. As(GS)(3) and [(GS)(2)AsSe](-) are chemically labile and have the potential to dissociate. However, arsenite (As(III)) +/- selenite (Se(IV)) transport was not detected in the absence of GSH or in the presence of the non-reducing GSH analog, ophthalmic acid, suggesting that the conjugates are the transported forms. The apparent K(m) values for [(GS)(2)AsSe](-) and As(GS)(3) were 1.7 and 4.2 microM, respectively, signifying high relative affinities. Membrane vesicles prepared from human erythrocytes, which express the MRP2-related MRP1/ABCC1, MRP4/ABCC4 and MRP5/ABCC5, transported As(GS)(3) in an MRP1- and ATP-dependent manner but did not transport [(GS)(2)AsSe](-). These results have important implications for the Se-dependent and -independent disposition of As.

Selenium or No Selenium- That Is the Question in Tumor Patients: A New Controversy

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more attention from both laypersons and expert groups. The interest of oncologists mainly focuses on the following clinical aspects: protection of normal tissues, sensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that it has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism, and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. In 2009, a significant benefit of sodium selenite supplementation-with no protection of tumor cells, which is often suspected by oncologists- was shown in a prospective randomized trial in gynecologic cancer patients undergoing radiation therapy. More recently, concerns arose from 2 large clinical prevention trials (NPC, SELECT) that selenium may increase the risk of developing type 2 diabetes. Despite obvious flaws in both studies and good counterarguments, controversy remains on the possible advantages and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are becoming obvious, even though further research is needed.

Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer’s disease

The aim of the present study is to evaluate the status of plasma essential trace elements magnesium (Mg), copper (Cu), zinc (Zn), iron (Fe) and selenium (Se) concentrations and their some related antioxidant enzyme activities, erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities in patients with Alzheimer’s disease (AD). Fifty patients with AD and fifty healthy control subjects were included in this study. Plasma Cu and Zn concentrations by atomic absorption spectrometry (AAS), plasma Mg and Fe concentrations by spectrophotometric methods and plasma Se concentrations by graphite furnace AAS were determined. Erythrocyte GPx, SOD and CAT activities were measured by spectrophotometric methods. Plasma Mg, Cu, Zn, Fe and Se levels and erythrocyte GPx, SOD and CAT activities were found to be significantly lower in patients with AD compared with controls. These results suggest that alterations in essential trace elements and their related enzymes may play a role in the etiopathogenesis of AD. Also, there is a defect in the antioxidant defense system, which may lead to oxidative damage in patients with AD. The changes in antioxidant enzyme activities may be secondary to the alterations in their cofactor concentrations.

Selenium in blood, semen, seminal plasma and spermatozoa of stallions and its relationship to sperm quality

The essential trace element selenium is indispensable for male fertility in mammals. Until now, little data existed regarding the relationship between selenium and sperm quality in the stallion. Selenium, or selenium-dependent glutathione peroxidase activity, was determined in red blood cells, semen, seminal plasma and spermatozoa, and the percentages of spermatozoa with progressive motility (PMS), intact membranes (PMI), altered (positive) acrosomal status (PAS) and detectable DNA damage, determined by the sperm chromatin structure assay, were evaluated in 41 healthy stallions (three samples each). The pregnancy rate per oestrus cycle (PRC) served as an estimation of fertility. An adverse effect on stallion fertility caused by low dietary selenium intake was excluded, as all stallions had sufficient selenium levels in their blood. Interestingly, no significant correlations (P > 0.05) between the selenium level in blood and the selenium level in seminal plasma or spermatozoa were found, suggesting that the selenium level in blood is no indicator of an adequate selenium supply for spermatogenesis. The selenium level in spermatozoa (nmol billion(-1)) was correlated with PMI, PMS and PAS (r = 0.40, r = 0.31 and r = -0.42, respectively; P </= 0.05), and the selenium concentration in spermatozoa (nmol g(-1)) was correlated with PRC (r = 0.40, P < 0.03). The results of the present study show that the determination of an adequate selenium status for the male equine reproduction requires the analysis of selenium in spermatozoa. Furthermore, selenium is associated with improved sperm quality and fertility in the stallion.

High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism

The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate metabolism in humans. However, increased plasma selenium levels might be both a consequence and a cause of diabetes. We summarize current evidence for an interference of selenium compounds with insulin-regulated molecular pathways, most notably the phosphoinositide-3-kinase/protein kinase B signaling cascade, which may underlie some of the pro- and anti-diabetic actions of selenium. Furthermore, we discuss reports of hyperinsulinemia, hyperglycemia and insulin resistance in mice overexpressing the selenoenzyme glutathione peroxidase 1. The peroxisomal proliferator-activated receptor gamma coactivator 1α represents a key regulator for biosynthesis of the physiological selenium transporter, selenoprotein P, as well as for hepatic gluconeogenesis. As proliferator-activated receptor gamma coactivator 1α has been shown to be up-regulated in livers of diabetic animals and to promote insulin resistance, we hypothesize that dysregulated pathways in carbohydrate metabolism and a disturbance of selenium homeostasis are linked via proliferator-activated receptor gamma coactivator 1α.

Selenium and thyroid

Inadequate supply of the essential trace element selenium (Se) has been associated with predisposition for, or manifestation of, various human diseases such as Keshan and Kashin-Beck disease, cancer, impaired immune function, neurodegenerative and age-related disorders and disturbances of the thyroid hormone axis. Se deficiency in combination with inadequate iodine contributes to the pathogenesis of myxedematous cretinism. The recent identification of various distinct selenocysteine-containing proteins, encoded by 25 human genes, provides information on the molecular and biochemical basis of beneficial and possible adverse effects of this trace element. The thyroid gland is among the human tissues with the highest Se content per mass unit similar to other endocrine organs and the brain. Selenoproteins involved in cellular antioxidative defence systems and redox control, such as the glutathione peroxidase (GPx) and the thioredoxin reductase (TxnRd) family, are involved in protection of the thyroid gland from excess hydrogen peroxide and reactive oxygen species produced by the follicles for biosynthesis of thyroid hormones. In addition, the three key enzymes involved in activation and inactivation of thyroid hormones, the iodothyronine deiodinases (DIO1,2,3), are selenoproteins with development, cell- and pathology-related expression patterns. While nutritional Se supply is normally sufficient for adequate expression of functional Dio enzymes with exception of long-term parenteral nutrition and certain diseases impairing gastrointestinal absorption of Se compounds, the nutritional Se supply for the protection of the thyroid gland and synthesis of some more abundant selenoproteins of the GPx and the TrxR family might be limiting their proper expression under (patho-)physiological conditions.

Selenium in oncology: from chemistry to clinics.

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed.

Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study

ObjectiveExperimental data suggest a protective role of the essential trace element selenium against cardiovascular disease (CVD), whereas epidemiological data remains controversial. We aimed to investigate the impact of serum selenium concentration in patients presenting with stable angina pectoris (SAP) or acute coronary syndrome (ACS) on long term prognosis. MethodsBaseline selenium concentration was measured in 1731 individuals (852 with SAP, and 879 with ACS). During a median follow-up of 6.1 years, 190 individuals died from cardiovascular causes. ResultsIn those ACS patients who subsequently died of cardiac causes, selenium levels were lower compared to survivors (61.0μg/L versus 71.5μg/L; P<0.0001). In a fully adjusted model, patients in the highest tertile of selenium concentration had a hazard ratio of 0.38 (95% CI: 0.16–0.91; P=0.03) as compared with those in the lowest. No association between selenium levels and cardiovascular outcome was observed in SAP. ConclusionsLow selenium concentration was associated with future cardiovascular death in patients with ACS.

Studies with Regard to the Apoptosis of Testicular Germ Cells in Rats Fed a Diet Enriched with Polyunsaturated Fatty Acids

The essential trace element selenium and polyunsaturated fatty acids (PUFA) have been used for the prevention of cancer. Both nutrients enhance the apoptosis of malignant cells and provide health benefits. However, an increased dietary intake of PUFA augments the susceptibility of lipid peroxidation and oxidative damage in many cells. So far, relatively few data are available about the interaction of selenium and PUFA in testis and thus a possible effect of both dietary components on the prevention of testicular cancer or on the apoptosis of testicular germ cells. Male germ cells in the rat contain most of the testicular phospholipid hydroperoxide glutathione peroxidase (PHGPx), mainly as the mitochondrial isoform of this selenoprotein (m-PHGPx). An experiment was therefore carried out to determine the action of fish oil, a nutrient rich in PUFA, on the testicular expression of PHGPx. Because the PHGPx formation remains nearly unchanged in the animals fed the PUFA-enriched diet, we conclude that no apoptosis of testicular germ cells is induced by an increased intake of this nutrient. The intake of fish oil in the selenium-deficient animal led to a markedly altered formation of several selenium-containing proteins, including sperm nuclei glutathione peroxidase (snGPx), also designated as the nuclear form of PHGPx (n-PHGPx), and a 10-kDa selenium-containing protein.

The brain selenoproteome: priorities in the hierarchy and different levels of selenium homeostasis in the brain of selenium‐deficient rats

The application of radionuclides for the localization of essential trace elements in vivo and the characterization of their binding proteins is a story of intermittently made improvements of the techniques used for their detection. In this study we present the use of neutron activation analysis and different autoradiographic imaging methods including real-time digital autoradiography to reveal new insights in the hierarchy of selenium homeostasis. Selenoproteins containing the essential trace element selenium play important roles in the CNS. Although the CNS does not show the highest selenium concentration in the case of selenium-sufficient supply in comparison with other organs, it shows a high priority for selenium uptake and retention in the case of dietary selenium deficiency. To characterize the hierarchy of selenium supply in the brain, in vivo radiotracer labeling with (75)Se in rats with different selenium status was combined with autoradiographic detection of (75)Se in brain tissue sections and (75)Se-labeled selenoproteins after protein separation by two-dimensional gel electrophoresis. This study demonstrates significant differences in the uptake of (75)Se into the brain of rats with different selenium status. A brain region-specific uptake pattern of the radiotracer (75)Se in selenium-deficient rats could be revealed and the CSF was identified as a key part of the brain selenium homeostasis.

Selenium and Inflammation: Underlying Anti-inflammatory Mechanisms

The essential trace element selenium (Se), in the form of selenoproteins, plays a pivotal role in the antioxidant defense system of the cell. There is evidence that Se may confer benefits in patients with inflammatory disease and even infectious diseases like HIV. Furthermore, in patients with severe sepsis, characterized by an increase in reactive oxygen species and low endogenous anti-oxidative capacity, as well as in patients with systemic inflammatory response syndrome, Se supplementation may reduce mortality and improve the clinical outcome, respectively. The nuclear factor kappa-B (NF-kappaB) signaling pathway has been associated with enhanced inflammatory response and its activation has been significantly correlated with interleukin-6 and TNF-alpha production. Selenium may inhibit the activation of NF-kappaB by modulating selenoprotein genes expression. Moreover, Se supplementation in chronic inflammation restores the depleted hepatic and serum Se levels by increasing selenoprotein biosynthesis leading to suppressed CRP production thereby attenuating the inflammatory process. Se increases shedding of L-selectin from monocytes while decreasing soluble L-selectin, which has been reported to be associated with high mortality in patients with sepsis. These mechanisms are likely to contribute to the modulatory effects of an increased Se status on the inflammatory response. This review evaluates some apparently key mechanisms of the anti-inflammatory action of selenium and advocates Se supplementation as a modulator of inflammatory response in infectious and autoimmune disease. Prospective, randomized, controlled studies must be performed to provide a greater degree of certainty.

Down‐regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice

The acute-phase response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in hepatocytes in culture. Analogous experiments were performed with mice transgenic for hepatocyte-specific human Sepp1 cDNA to verify this hypothesis. Similar kinetics and effect sizes of Sepp1 expression were observed as before in wild-type mice. We conclude that hepatic translation of Sepp1 mRNA is specifically impaired during the APR. This deficit disrupts regular Se metabolism, transport, and supply to peripheral tissues and likely aggravates the pathological status.

Strategy for the Utilization of an Essential Trace Element Selenium by Marine Phytoplanktons.

Strategy for the Utilization of an Essential Trace Element Selenium by Marine Phytoplanktons.