Concentration Of Selenoprotein Research Articles

Selenoprotein P, peroxiredoxin-5, renalase, and total antioxidant status in patients with suspected obstructive sleep apnea

PurposeThe aim of this study was to investigate the relationship between selenoprotein P, peroxiredoxin-5, renalase, total antioxidant status (TAS), mean blood pressure (mBP), and apnea-hypopnea index (AHI).MethodsThe study group consisted of 112 patients hospitalized to verify the diagnosis of obstructive sleep apnea (OSA). The inclusion criteria were consent to participate in the study and age ≥ 18 years. Patients with active proliferative disease, severe systemic diseases, or mental diseases were excluded from the study. Each patient underwent full polysomnography and had blood pressure measured. Blood samples were collected and laboratory test was performed.ResultsAmong 112 patients enrolled, there was a statistically significant negative linear correlation between blood pressure values (sBP, dBP, mBP) and selenoprotein P, renalase, and TAS levels. Similarly, there was a negative linear correlation between AHI and selenoprotein P, renalase, and TAS levels, but none between AHI and peroxiredoxin-5. Based on the obtained regression models, higher selenoprotein P, peroxiredoxin-5, and renalase levels were independently associated with higher TAS. Lower mBP values were independently associated with the use of antihypertensive drugs, higher TAS, and younger age. Male gender, higher BMI, and higher mBP were independently associated with higher AHI.ConclusionsHigher concentrations of selenoprotein P, peroxiredoxin-5, and renalase were associated with higher TAS, which confirms their antioxidant properties. There was an indirect connection between tested antioxidants and blood pressure values.

Selenoprotein P concentrations and risk of progression from mild cognitive impairment to dementia

There is a growing literature investigating the effects of selenium on the central nervous system and cognitive function. However, little is known about the role of selenoprotein P, the main selenium transporter, which can also have adverse biological effects. We conducted a prospective cohort study of individuals aged 42–81 years who received a clinical diagnosis of mild cognitive impairment. Using sandwich ELISA methods, we measured full-length selenoprotein P concentrations in serum and cerebrospinal fluid to assess the relation with dementia incidence during a median follow-up of 47.3 months. We used Cox proportional hazards regression and restricted cubic splines to model such relation. Of the 54 participants, 35 developed dementia during follow-up (including 26 cases of Alzheimer’s dementia). Selenoprotein P concentrations in serum and cerebrospinal fluid were highly correlated, and in spline regression analyses they each showed a positive non-linear association with dementia risk, particularly after excluding dementia cases diagnosed within 24 months of follow-up. We also observed differences in association according to the dementia subtypes considered. Risk ratios of dementia peaked at 2–6 at the highest levels of selenoprotein P, when compared to its median level, also depending on matrix, analytical methodology and dementia subtype. Findings of this study, the first to assess selenoprotein P levels in the central nervous system in vivo and the first to use a prospective study design to evaluate associations with dementia, suggest that higher circulating concentrations of selenoprotein P, both in serum and cerebrospinal fluid, predict progression of MCI to dementia. However, further confirmation of these findings is required, given the limited statistical precision of the associations and the potential for residual confounding.

Digging deeper into the mother-offspring transfer of selenium through human breast milk

Selenoprotein P contains most of the selenium in plasma and favours selenium retention in the brain over other organs. Recently, the presence of selenoprotein P in human breast milk has been demonstrated, filling the gap around the mother-offspring transfer of selenium during lactation and through cord serum. In this work, selenometabolites and selenoproteins have been accurately determined in human breast milk and cord and maternal sera. Using a heteroatom tagged proteomic method, twenty mother-child couples were analysed. The mean total concentration in maternal serum was 90 ± 10 ng Se g−1 (1.33 and 1.52-fold higher than that in cord serum and human breast milk, respectively). The concentration of selenoprotein P (ng Se g−1) follows the order: maternal serum (57.1 ± 8.8) > cord serum (33.6 ± 4.2) > breast milk (18.8 ± 5.1). Glutathione peroxidase was mainly transferred by breast milk, selenometabolites were transferred by breast milk and cord serum and selenocystamine was only present in breast milk.

Selenoprotein P as a Marker of Comorbid Development of Nonalcoholic Fatty Liver Disease and Hypertension

Nonalcoholic fatty liver disease (NAFLD) and hypertension are one of the most widespread diseases in world population. They share common risk factors and aspects of pathogenesis, which include inflammation, oxidative stress, insulin resistance, dyslipidemia etc. Violations of hepatokines, such as Selenoprotein P (Sel P), can directly influence endothelial function and vascular remodeling. Selenium is important trace element, which takes part in numerous processes of organism function. Those include brain function, development of innate and acquired immunity, antioxidant protection etc. Moreover, it was found that this trace element plays important role in development of cardiovascular pathology and diabetes by triggering development of insulin resistance, dyslipidemia, obesity and hypertension — components of metabolic syndrome. Those factors also induce development of nonalcoholic fatty liver disease. Several researches indicate that Selenium deficiency leads to activation of oxidative stress and inflammation, which leads to endothelial dysfunction and increasing of arterial stiffness — one of the main factors of development of hypertension. Noteworthy, increased concentration of Selenoprotein P (molecule that contains the highest amount of Selenium and can act as its indicator) violates signaling of insulin and glucose metabolism in liver, which leads to diabetes development. In NAFLD patients increased Sel P concentrations correlate with abdominal obesity and insulin resistance. According to researches, increased concentration of Sel P increases risk of NAFLD development in 7.5 times. Described peculiarities allow using Sel P as prognostic marker of development both NAFLD and hypertension due to its effects on metabolic syndrome development.

Effect of maternal organic selenium supplementation during pregnancy on sow reproductive performance and long-term effect on their progeny.

Selenium (Se) is an essential trace element for animals and exists in nature in both inorganic and organic forms. Although organic Se is more bioavailable than inorganic Se, there are inconsistent reports on the effect of organic Se on the reproductive performance of sows. This study was conducted to investigate the effect of maternal organic Se (2-hydroxy-4-methylselenobutanoic [HMSeBA]) supplementation on reproductive performance and antioxidant capacity of sows, and the long-term effect on the growth performance and antioxidant capacity of their offspring with or without lipopolysaccharide (LPS) challenge. The experimental design used in this study was a completely randomized design; 45 Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (Control, basal diet, n = 15), sodium selenite (Na2SeO3)-supplemented diet (Na2SeO3, basal diet + 0.3 mg Se/kg Na2SeO3, n = 15), and HMSeBA-supplemented diet (HMSeBA, basal diet + 0.3 mg Se/kg HMSeBA, n = 15). On day 21 of age, male offspring from each group were injected with LPS or saline (n = 6). As compared with the control group, maternal HMSeBA supplementation increased the number of total born piglets, while decreased birth weight (P < 0.05). In the first week of lactation, maternal HMSeBA supplementation increased litter weight gain compared with the Na2SeO3 group (P < 0.05) and increased the average daily gain of piglets compared with the control group and Na2SeO3 group (P < 0.05). Meanwhile, maternal HMSeBA supplementation decreased piglet birth interval as compared with the control group and Na2SeO3 group (P < 0.05). Besides, plasma glutathione peroxidase (GSH-Px) activity was higher in the HMSeBA group on farrowing 0 min and 90 min, while malondialdehyde (MDA) concentration was lower on farrowing 0, 90, and 135 min than those in the control group (P < 0.05). In addition, maternal HMSeBA supplementation increased the concentration of selenoprotein P (SELENOP) in colostrum compared with the control group (P < 0.05). Further study revealed that the LPS-challenged HMSeBA group had higher GSH-Px and total antioxidant capacity and lower MDA in weaning piglets compared with the LPS-challenged control group (P < 0.05). Taken together, maternal HMSeBA supplementation increased the number of total born piglets, shortened the duration of farrowing, improved the antioxidant capacities of sows and their offspring, and improved the growth performance of suckling pigs at the first week of lactation. Thus, HMSeBA supplementation during gestation has the potentiality to produce more kilogram of meat.

Abstract 13678: Serum Hepatokine Selenoprotein P is Upregulated by Hepatic Hypoperfusion and Predicts Adverse Prognosis in Heart Failure Patients

Introduction: Cardiac and multiple organ network is involved in the pathophysiology of heart failure (HF). Hepatokines, which are produced and secreted from the liver, have regulatory functions in the peripheral tissues. However, the interaction between the heart and liver or clinical relevance of hepakokines in HF remains poorly understood. The present study aimed to elucidate the clinical significance of hepatokine selenoprotein P in HF. Methods and Results: We enrolled 250 participants including 171 hospitalized patients with HF and 79 control subjects. The serum concentration of selenoprotein P was measured by an enzyme-linked immunosorbent assay. We found that the serum selenoprotein P levels in HF patients were significantly higher than those in controls (14.8 ± 7.5 vs. 8.4 ± 4.6 mg/L, P&lt;0.01). Next, the HF patients were categorized into 4 groups based on the hepatic hemodynamics assessed by abdominal-ultrasonography, which determined liver congestion by shear wave elastography (liver-SWE, &gt;1.33 m/s) and liver hypoperfusion by peak systolic velocity of the celiac artery (celiac-PSV, &lt;62.4 cm/s). Selenoprotein P levels were significantly upregulated in patients with liver hypoperfusion compared to patients with liver congestion ( Figure A ). Selenoprotein P was negatively correlated with celiac-PSV (P&lt;0.01), cardiac output (P&lt;0.01), and left ventricular stroke volume (P=0.03), whereas no correlations were observed between selenoprotein P and indices of congestion such as liver-SWE and right atrial pressure. Kaplan-Meier analysis demonstrated that a higher selenoprotein P group showed a lower event-free rate from re-hospitalization due to worsening HF ( Figure B ). Conclusion: Upregulation of liver-derived selenoprotein P was associated with hepatic hypoperfusion, not hepatic congestion, and related to the adverse prognosis in HF. Selenoprotein P may be a novel molecule involved in the cardio-hepatic interaction.

518: The risk of pregnancy-associated hypertension in pregnant women with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for cardiovascular diseases in later life. Although the biologic mechanism is not well understood, it likely involves metabolic factors, inflammatory reactions, and endothelial dysfunction, all of which are known pathophysiologic factors in the development of pregnancy- associated HTN, including preeclampsia. However, the risk of pregnancy-associated HTN in pregnant women with NAFLD has not been well established. This study examines the risk of pregnancy-associated HTN in pregnant women with NAFLD. This is a secondary analysis of a large prospective cohort study of healthy Korean women with a singleton pregnancy designed to examine the risk of gestational diabetes in women with NAFLD. Liver ultrasound was performed in all cases at 10-14 weeks of gestation and the degree of hepatic steatosis classified as Grade 0-3. At the time of liver ultrasound, maternal blood was taken and measured for selenoprotein P, a hepatokine that has been independently associated with NAFLD and cardiovascular disease. Pregnancy-associated HTN was defined as the development of gestational hypertension, preeclampsia, or eclampsia. Among 877 enrolled subjects, the risk of pregnancy-associated HTN increased significantly in patients with NAFLD (Fig 1). Grade 2-3 steatosis at 10-14 weeks was a significant risk factor for the development of pregnancy- associated HTN, even after adjustment for metabolic risk factors (BMI, fasting glucose). The concentration of selenoprotein P was significantly higher in women with NAFLD vs those without NAFLD at 10-14 weeks (p=0.001), and was also significantly increased in women who subsequently developed pregnancy-associated HTN vs those that did not (p<0.001) (Fig 2). Sonographic evidence of NAFLD at 10-14 weeks is an independent risk factor for pregnancy- associated HTN. Circulating selenoprotein P levels are increased in patients with NAFLD, which may be linked to the development of pregnancy-associated HTN.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Impacts of selenium and vitamin E supplementation on mRNA of heat shock proteins, selenoproteins and antioxidants in broilers exposed to high temperature

The study was carried out to investigate the effect of dietary selenium (Se) and vitamin E (VE) supplementation on mRNA level of heat shock proteins, selenoproteins, and antioxidant enzyme activities in the breast meat of broilers under summer heat stress conditions. A total of 200 male broilers (Ross 308) of 1 day age were randomly separated into 4 groups in a complete randomized design and were given a basal diet (Control, 0.08 mg Se/kg diet) or basal diet supplemented with VE (250 mg/kg VE), sodium selenite (0.2 mg/kg Se), or Se + VE (0.2 mg/kg Se + 250 mg/kg VE) to investigate the expression of key antioxidant and heat shock protein (HSP) genes under high temperature stress. Dietary Se, VE and Se + VE significantly enhanced the activities and mRNA levels of catalase as well as superoxide dismutase (SOD) but decreased the mRNA levels of HSP70 and HSP90. Se alone or combined with VE increased the concentration of selenoprotein P and selenoproteins mRNA level and decreased the expression of HSP60. In addition, Se and Se + VE significantly enhanced the glutathione peroxidase (GPx) activity and the expression of GPx1 and GPx4 in breast muscle tissues. It is noteworthy that all the treatments significantly decreased malondialdehyde (MDA) level in the breast meat. Overall results showed that Se in combination with VE has maximal effects to mitigate heat stress. Based on given results it can be recommended that Se + VE are a suitable dietary supplement for broilers to ameliorate the negative effects of summer heat stress conditions.

Biomarkers of selenium status and antioxidant effect in workers occupationally exposed to mercury

The present observation based research was designed to evaluate the influence of occupational human exposure to metallic mercury (Hg°) vapor on the biomarkers of selenium status involved in the antioxidant defense system. For this purpose we determined Hg and selenium (Se) concentrations in body fluids, the markers of antioxidant effect measured as an activity of Se-dependent enzymes (red blood cell and plasma glutathione peroxidase: GPx1-RBC and GPx3-P), concentration of selenoprotein P in the plasma (SeP-P) and total antioxidant activity in the plasma (TAA-P) in 131 male workers from a chloralkali plant exposed to Hg° and 67 non-exposed males (control group). The mRNA expression levels of glutathione peroxidases (GPX1, GPX3), selenoprotein P (SEPP1), thioredoxin reductase 1 (TRXR1), thioredoxin 1 (TRX1), peroxiredoxins (PRDX1, PRDX2) were also examined in the leukocytes of peripheral blood. Hg concentration in the blood (Hg-B) and urine (Hg-U) samples was determined using the thermal decomposition amalgamation/atomic absorption spectrometry (TDA-AAS) method and Se concentrations in plasma (Se-P) and urine (Se-U) using the inductively coupled plasma mass spectrometry (ICP-MS) method. Activities of GPx1-RBC, GPx3-P and TAA-P were determined using the kinetic and spectrophotometric method, respectively. Gene expression analysis was performed using the quantitative Real-Time PCR.The results showed significant higher Hg levels among the Hg°–exposed workers in comparison to control group (12-times higher median for Hg-B and almost 74-times higher median for Hg-U concentration in chloralkali workers). Se-P was also significantly higher (Me (median): 82.85 μg/L (IQR (interquartile range) 72.03–90.28 μg/L) for chloralkali workers vs. Me: 72.74 μg/L (IQR 66.25-80.14 μg/L) for control group; p = 0.0001) but interestingly correlated inversely with Hg-U in chloralkali workers suggesting depletion of the Se protection among the workers with the highest Hg-U concentration. The mRNA level for GPX1, PRXD1 were markedly but significantly higher in the workers compared to the control group. Moreover, concentrations of Hg-B and Hg-U among the workers were significantly positively correlated with the levels of selenoprotein P at both the mRNA and selenoprotein levels. In the multivariate model, after adjusting to cofounders (dental amalgam fillings, age, BMI, job seniority time, smoking), we confirmed that Hg-U concentration was inversely correlated with genes expression of TRXR1.This is the first comprehensive assessment of the impact of occupational exposure of workers to Hg° at both the mRNA and selenoprotein levels, with investigation of fish intake obtained by means of a questionnaire. These findings suggest that exposure to Hg° alters gene expression of the antioxidant enzymes and the level of Se-containing selenoproteins.

Selenium, selenoproteins and human health: a review.

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.

Production and Application of Monoclonal Antibodies to Human Selenoprotein P.

Selenoprotein P is a selenium-rich extracellular protein and is the major selenoprotein in plasma. Although the biological function of selenoprotein P has not been established, we have recently shown that selenoprotein P has phospholipid hydroperoxide glutathione peroxidase-like activity. To study the structure and function of selenoprotein P, we produced monoclonal antibodies against human selenoprotein P. Immunization of rats with purified selenoprotein P was followed by hybridization, cloning, and the establishment of eleven hybridomas producing specific antibodies against human selenoprotein P. With the addition of six kinds of insoluble rat anti-human selenoprotein P monoclonal antibodies to human plasma, the selenium concentration of the supernatant was decreased to 47% of the control. This suggests that selenoprotein P constituted 53% of total plasma selenium. Western blot analysis of the immunoprecipitate from human plasma showed that the antibodies specifically bound to a 69 kDa protein, representing selenoprotein P. Next, we developed an enzyme-linked immunosorbent assay for selenoprotein P using two monoclonal antibodies. The plasma concentration of selenoprotein P in 77 normal individuals was 5.3 ± 1.1 μg/ml. Because preferential depletion of selenoprotein P by low density lipoprotein (LDL)-apheresis has been reported, we next measured selenoprotein P concentration of plasma samples from patients before and after LDL-apheresis. We confirmed that the plasma concentration of selenoprotein P was decreased from 5.7 to 2.3 μg/ml by LDL-apheresis. This result shows that this assay provides a reliable means of measuring the content of selenoprotein P in plasma.

Binding of selenoprotein P to heparin: characterization with surface plasmon resonance.

The binding of selenoprotein P to glycosaminoglycans using heparin as a model compound was studied by surface plasmon resonance. It was found that heparin contains two binding sites for selenoprotein P, a high-affinity, low-capacity site (Kd approximately 1 nM) and a low-affinity, high-capacity site (Kd approximately 140 nM). Binding at both sites is sensitive to pH and ionic strength, and the high-affinity site is abolished by histidine carbethoxylation with diethylpyrocarbonate. The pH and salt dependence of binding suggests electrostatic interactions with heparin. The concentrations of selenoprotein P in plasma (approximately 50 nM) are sufficiently high to facilitate binding of selenoprotein P to proteoglycans on the vascular endothelium, and this may contribute to the formation of a protective barrier against oxidants such as peroxynitrite or hydroperoxides.

Orphan selenoproteins.

Selenoproteins contain selenium in stoichiometric amounts. Most are synthesized by a process that decodes UGA codons as selenocysteine. Twelve animal selenoproteins have been characterized, and biochemical functions have been described for all but three. Two of these "orphan" selenoproteins are discussed in this paper. Selenoprotein P is an extracellular glycoprotein that contains multiple selenocysteines. It binds heparin and associates with endothelial cells. Two isoforms have been identified. Plasma concentration of selenoprotein P correlates with protection against diquat liver injury, suggesting that the protein protects against oxidant injury. Selenoprotein W is a small intracellular protein that contains one selenocysteine. It binds glutathione and has been suggested to function in oxidant defense. The postulated oxidant defense properties of these selenoproteins are consistent with the facile thiol-redox properties of selenocysteine. It can be predicted that more proteins will be discovered that take advantage of the chemical properties of selenium.

Orphan selenoproteins

Selenoproteins contain selenium in stoichiometric amounts. Most are synthesized by a process that decodes UGA codons as selenocysteine. Twelve animal selenoproteins have been characterized, and biochemical functions have been described for all but three. Two of these “orphan” selenoproteins are discussed in this paper. Selenoprotein P is an extracellular glycoprotein that contains multiple selenocysteines. It binds heparin and associates with endothelial cells. Two isoforms have been identified. Plasma concentration of selenoprotein P correlates with protection against diquat liver injury, suggesting that the protein protects against oxidant injury. Selenoprotein W is a small intracellular protein that contains one selenocysteine. It binds glutathione and has been suggested to function in oxidant defense. The postulated oxidant defense properties of these selenoproteins are consistent with the facile thiol-redox properties of selenocysteine. It can be predicted that more proteins will be discovered that take advantage of the chemical properties of selenium. BioEssays 21:231–237, 1999. © 1999 John Wiley & Sons, Inc.

Selenium Influences Tissue Levels of Selenoprotein W in Sheep1–4

Because selenium increases the levels of other selenoproteins, the influence of this element on selenoprotein W was examined in wether sheep fed either a low selenium diet (0.02 mg/kg) or the same diet supplemented with 3 mg selenium as selenite per kilogram diet. Muscle biopsies were taken initially and at 3.5, 7.0 and 10.5 wk. The sheep were killed after the last muscle biopsy and samples from nine tissues were taken. Selenoprotein W was determined in tissues by Western blots with a polyclonal antibody against a synthetic peptide based on the protein sequence of the homologous rat selenoprotein W. In supplemented sheep, muscle selenoprotein W was significantly increased over initial levels (P < 0.05) at 7 wk and afterwards, whereas in sheep consuming the low selenium diet, muscle selenoprotein W levels declined significantly (P < 0.05) after 10.5 wk. This selenoprotein was found in various amounts in all tissues examined. The highest levels of selenoprotein W were found in skeletal muscles and heart and the lowest was found in liver. Except for selenoprotein W in brain, the concentrations of selenoprotein W, selenium and glutathione peroxidase activity were significantly higher (P < 0.05) in all tissues from supplemented sheep than in those from unsupplemented sheep. The selenoprotein W levels in brains of the two groups were not significantly different. Thus, selenoprotein W levels in all tissues of sheep except the brain are sensitive to selenium status.

Response of rat selenoprotein P to selenium administration and fate of its selenium

Selenoprotein P is a glycoprotein that contains greater than 60% of the selenium in rat plasma. Physiological experiments were undertaken to gain insight into selenoprotein P function. Selenium-deficient rats were injected with doses of selenium ranging from 25 to 200 micrograms/kg, and the appearance of selenoprotein P was compared with the appearance of glutathione peroxidase activity in plasma and in liver. Selenoprotein P concentration increased to 35% of control by 6 h, whereas glutathione peroxidase activity increased minimally or not at all. Moreover, in rats given 100 and 200 micrograms selenium/kg, selenoprotein P reached 75% of its concentration in control rats at 24 h, whereas glutathione peroxidase activity reached only 6% of control. Cycloheximide pretreatment blocked the appearance of selenoprotein P in response to selenium injection. Male and female rats had similar concentrations of selenoprotein P. Partially purified selenoprotein P and plasma glutathione peroxidase labeled with 75Se were administered intravenously to selenium-deficient and control rats. 75Se given as selenoprotein P disappeared more rapidly from plasma than did 75Se given as glutathione peroxidase. Selenium deficiency did not significantly affect 75Se disappearance from plasma. At 2 h, brain, but not other tissues, took up more 75Se in selenium-deficient rats than in control rats when 75Se was given as selenoprotein P. This suggests that brain has a specific uptake mechanism for selenium given in the form of selenoprotein P. These results demonstrate that several physiological properties distinguish selenoprotein P from glutathione peroxidase. However, they do not clearly indicate its function.

Selenium and amino acid composition of selenoprotein P, the major selenoprotein in rat serum.

Selenoprotein P is the second plasma selenoprotein to be purified. It is a glycoprotein and has been shown to be distinct from plasma glutathione peroxidase. This study characterizes selenoprotein P further. Deglycosylation of the protein shifts its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from Mr 57,000 to Mr 43,000, indicating it has a substantial carbohydrate component. Measurement of selenium indicates a selenium content of 7.5 +/- 1.0 atoms/molecule based on a polypeptide weight of 43,000. Amino acid analysis accounts for all the selenium as selenocysteine. The protein is also rich in cysteine (17 residues) and histidine (23 residues). Fragmentation of selenoprotein P by trypsin and by cyanogen bromide produces peptides with varying selenium content. This indicates that selenium-rich regions of the protein exist. The concentration of selenoprotein P determined by radioimmunoassay in serum from control rats is 26.3 +/- 4.5 micrograms/ml and in serum from selenium-deficient rats it is 2.7 +/- 0.8 micrograms/ml. Depletion of selenoprotein P from control serum using an immunoaffinity column indicates that over 60% of serum selenium in the rat is contained in this protein. These results demonstrate that selenoprotein P is the major form of selenium in rat serum. It is the first selenoprotein described which has more than one selenium atom/polypeptide chain.

Dietary Selenium Intake Controls Rat Plasma Selenoprotein P Concentration

The purpose of this study was to determine the effect of dietary selenium on selenoprotein P concentration. Selenoprotein P was quantitated in plasma by radioimmunoassay. Selenium-dependent glutathione peroxidase activity in plasma and liver 105,000 x g supernatant was measured for comparison. Weanling male rats were fed a selenium-deficient diet or a control diet that contained 0.5 mg selenium/kg as Na2SeO4. The concentration of selenoprotein P fell at approximately the same rate in the rats fed the selenium-deficient diet as did plasma glutathione peroxidase activity. Groups of weanling rats were fed different levels of selenium for 8 wk. Selenoprotein P concentration was proportional to dietary selenium level up to 0.1 mg/kg and was a greater percentage of control values than was glutathione peroxidase activity. No increment in selenoprotein P concentration occurred between 0.1 and 0.5 mg selenium/kg diet. These results indicate that the concentration of selenoprotein P in the plasma is directly dependent on selenium supply in the diet up to 0.1 mg/kg. There is overlap between the dietary selenium ranges in which selenoprotein P concentration and glutathione peroxidase activity increase, but the selenoprotein P range is lower than the glutathione peroxidase range.