Selenium Deficiency in COVID-19-A Possible Long-Lasting Toxic Relationship.

In the last two years, there has been a surge in the number of publications on the trace element selenium (Se) and selenocysteine-containing selenoproteins in human health, largely due to the pandemic and the multiple roles that this micronutrient and Se-dependent selenoproteins play in various aspects of the disease [...].

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity.

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

Association between creatine kinase activity, oxidative stress and selenoproteins mRNA expression changes after Brazil nut consumption of patients using statins.

BACKGROUND & AIMS: Although the mechanisms by which statins promote muscle disorders remain unclear, supplementation with dietary antioxidants may mitigate statins' side effects. This study aimed to investigate whether the consumption of Brazil nuts modulates serum creatine kinase (CK) activity in patients regularly using statins. METHODS: The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients in regular use of statins were divided according to CK activity levels (G1: increased or G2: normal) and received one unit of Brazil nut daily for 3 months. Body composition, blood selenium (Se) concentrations, erythrocyte glutathione peroxidase (GPX) activity, oxidative stress parameters, and CK activity were evaluated before and after supplementation. RESULTS: In both groups, supplementation with one Brazil nut daily for 3 months contributed to achieve decreased levels of CK activity in serum, with positive changes in plasma and erythrocyte Se concentrations (p < 0.0001), and increased levels of GPX activity. Among the parameters related to curbing of oxidative stress, we observed reduced levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in both groups after supplementation. We also found a moderately negative association between CK and GPX activity (r = -41; p < 0.02). Expression of selenoproteins GPX1, SELENOP, and SELENON after Brazil nut supplementation was unchanged. CONCLUSION: Brazil nut consumption enhanced the control of CK activity by improving oxidative stress biomarkers in patients using statins but did not modulate mRNA expression of selenoproteins.

Absolute quantification of selenoproteins and selenometabolites in lung cancer human serum by column switching coupled to triple quadrupole inductively coupled plasma mass spectrometry.

One of the most important causes of the high mortality rate and low life expectancy of lung cancer is the detection at advanced stages. Thus, there is an urgent need for early diagnosis and the search of new selective biomarkers. Selenium is an important constituent of selenoproteins and a powerful antioxidant able to protect against cancer. In this work, the absolute quantification of selenium in selenoproteins and the total content in selenometabolites has been performed for the first time in serum from lung cancer patients (LC) and healthy controls (HC). To this end, a method for the simultaneous speciation of selenoproteins using size exclusion chromatography (SEC) and affinity chromatography (AF) with detection by ICP-QQQ-MS, and quantification by isotopic dilution (IDA) (SEC-AF-HPLC-SUID-ICP-QQQ-MS) was developed to determine the selenium concentration in eGPx, SEPP1 and SeAlb, as well as total selenometabolites, to find alterations that may serve as biomarkers of this disease. In the same way, a method based on anion-exchange chromatography coupled to ICP-QQQ-MS was developed to quantify selenometabolites (SeCys2, SeMeSeCys, SeMet, selenite and selenate) in the same LC and HC serum samples. The results showed that the averaged concentrations of selenium in eGPx, SeAlb and selenite were significantly higher in LC patients (LC (eGPx: 21.24 ± 0.77 ng g-1; SeAlb: 49.56 ± 3.16 ng g-1 and Se(IV): 6.20 ± 1.22 ng g-1) than in HC group (eGPx: 16.96 ± 0.53 ng g-1; SeAlb: 38.33 ± 2.66 ng g-1 and Se(IV): 3.56 ± 0.55 ng g-1). In addition, the ratios between selenoproteins and selenometabolites have been calculated for the first to study their potential use as LC biomarkers. The rates eGPx/SEPP1, SEPP1/SeAlb, eGPx/Se(IV) and SEPP1/Se(IV) were significantly different between LC and HC groups.

Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children?

PURPOSE: Hepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children. PATIENTS AND METHODS: The cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). RESULTS: The concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in 1H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant. CONCLUSIONS: FGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children.

Relation of selenium status to neuro-regeneration after traumatic spinal cord injury.

INTRODUCTION: The trace element selenium (Se) is crucial for the biosynthesis of selenoproteins. Both neurodevelopment and the survival of neurons that are subject to stress depend on a regular selenoprotein biosynthesis and sufficient Se supply by selenoprotein P (SELENOP). HYPOTHESIS: Neuro-regeneration after traumatic spinal cord injury (TSCI) is related to the Se status. STUDY DESIGN: Single-centre prospective observational study. PATIENTS AND METHODS: Three groups of patients with comparable injuries were studied; vertebral fractures without neurological impairment (n = 10, group C), patients with TSCI showing no remission (n = 9, group G0), and patients with remission developing positive abbreviated injury score (AIS) conversion within 3 months (n = 10, group G1). Serum samples were available from different time points (upon admission, and after 4, 9 and 12 h, 1 and 3 days, 1 and 2 weeks, and 1, 2 and 3 months). Serum trace element concentrations were determined by total reflection X-ray fluorescence, SELENOP by ELISA, and further parameters by laboratory routine. RESULTS: Serum Se and SELENOP concentrations were higher on admission in the remission group (G1) as compared to G0. During the first week, both parameters remained constant in C and G0, whereas they declined significantly in the remission group. Similarly, the concentration changes between admission and 24 h were most pronounced in this group of recovering patients (G1). Binary logistic regression analysis including the delta of Se and SELENOP within the first 24 h indicated an AUC of 90.0% (CI: 67.4%-100.0%) with regards to predicting the outcome after TSCI. CONCLUSION: A Se deficit might constitute a risk factor for poor outcome after TSCI. A dynamic decline of serum Se and SELENOP concentrations after admission may reflect ongoing repair processes that are associated with higher odds for a positive clinical outcome.

Maternal selenium status is profoundly involved in metabolic fetal programming by modulating insulin resistance, oxidative balance and energy homeostasis.

PURPOSE: High and low levels of selenium (Se) have been related to metabolic disorders in dams and in their offspring. Their relationship to oxidative balance and to AMP-activated protein kinase (AMPK) is some of the mechanisms proposed. The aim of this study is to acquire information about how Se is involved in metabolic programming. METHODS: Three experimental groups of dam rats were used: control (Se: 0.1 ppm), Se supplemented (Se: 0.5 ppm) and Se deficient (Se: 0.01 ppm). At the end of lactation, the pups' metabolic profile, oxidative balance, Se levels, selenoproteins and IRS-1 hepatic expression, as well as hepatic AMPK activation were measured. RESULTS: The experimental groups present deep changes in Se homeostasis, selenoproteins and IRS-1 hepatic expression, oxidative balance, AMPK activation ratio and insulin levels. They do, however, have different metabolic profiles. CONCLUSIONS: High- and low-Se diets are linked to insulin resistance, yet the mechanisms involved are completely opposite.

Associations and interactions between variants in selenoprotein genes, selenoprotein levels and the development of abdominal aortic aneurysm, peripheral arterial disease, and heart failure.

BACKGROUND: Little is known on the role of selenoprotein genes in cardiovascular disease. This study examines the associations of the SEPP1, SELENOS, TXNRD1, TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype. METHODS: 564 patients with AAA, 400 patients with AIOD, and 543 controls were enrolled and characterized for coronary artery disease, myocardial infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence of peripheral arterial disease (PAD) was examined. Genotypes were determined using TaqMan-based assays. Selenoprotein concentration was assessed using the ELISA method. RESULTS: The SELENOS rs34713741T, SEPP1 rs3877899A, and GPX4 rs713041T alleles were related to a 30-60% increase in the AIOD/PAD risk in the recessive or dominant model (all associations at P < .05). The SEPP1 rs3877899A allele was a protective factor for the development of AAA without concomitant PAD (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD. The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were observed, including the multiplicative interaction between the SELENOS rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for carriers, P = .013) and increased SeP concentrations; SeP level ≥8.5 mg/mL caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated with BMI (r = -0.575, P < .0001). CONCLUSIONS: Our results provide evidence that selenoprotein polymorphisms constitute a risk factor for HF and peripheral atherosclerosis, but prevent the development of AAA. Excessive weight might result in reduced antioxidant reserve efficiency in AAA. Validation studies are required to establish whether SeP concentration may be a marker for HF.

Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

BACKGROUND: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. METHODS: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. RESULTS: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). CONCLUSIONS: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.

Simultaneous Speciation of Selenoproteins and Selenometabolites in Plasma and Serum.

Selenium is an essential element incorporated to different proteins with important biological functions in connection to antioxidant activity, cancer-protective properties, neurodegenerative pathologies, and prevention of effects of diabetes, among others. In addition, selenoamino acids play a basic role in the global equilibrium of key selenium-biomolecules synthesis, including selenoprotein P, selenoalbumin, and glutathione peroxidase. Homeostasis of these selenium-containing biomolecules involves different organs in living organisms including human, and bloodstream is the connection fluid in this process. Therefore, it is very important to have an analytical methodology suitable for selenium proteins and metabolites speciation in serum and plasma samples. For this purpose, a simultaneous speciation method for Se-containing biomolecules in serum/plasma is described on the basis of in series three-dimensional chromatography: size exclusion, affinity, and anion exchange high performance liquid chromatography (3D/SE-AF-AEC-HPLC), using different columns of each type and hyphenation to inductively coupled plasma-(quadrupole) mass spectrometry (ICP-MS). The method allows the quantitative simultaneous analysis of selenoprotein P (SeP), extracellular glutathione peroxidase (eGPx), selenoalbumin (SeAlb), selenite, and selenate in serum (from human and mouse) using species-unspecific isotope dilution (SUID). In addition, a simplified two-dimensional approach (2D/SE-AF-HPLC-SUID-ICP-MS) is described when selenium metabolites are globally analyzed. The method provides detection limits in the range 0.2-1.3 ng of Se g-1 and avoids typical interferences in this matrix from chloride and bromide with a chromatographic runtime less than 35 min.

Identification of Genetic Disorders Causing Disruption of Selenoprotein Biosynthesis.

Disorders of selenoprotein biosynthesis in humans, due to mutations in three genes (SECISBP2, TRU-TCA1-1, and SEPSECS) involved in the selenocysteine insertion pathway, have been described. Patients with SECISBP2 and TRU-TCA1-1 defects manifest a multisystem disorder with a biochemical signature of abnormal thyroid function tests due to the impaired activity of deiodinase selenoenzymes, myopathic features linked to SEPN1 deficiency and phenotypes resulting from increased levels of reactive oxygen species attributable to lack of antioxidant selenoenzymes. In patients harboring SEPSECS mutations, severe, progressive, cerebello-cerebral atrophy (pontocerebellar hypoplasia type 2D) dominates the phenotype and it is not known whether the disorder is associated with thyroid dysfunction.

Effect of Low-Selenium/High-Fat Diet on Pig Peripheral Blood Lymphocytes: Perspectives from Selenoproteins, Heat Shock Proteins, and Cytokines.

The aim of the present study was to clarify the effect of low selenium (Se)/high fat on the mRNA expression of selenoproteins, heat shock proteins (HSPs) and cytokines in pig peripheral blood lymphocytes. Forty crossbred boar piglets with healthy lean body weights of 10 kg were randomly divided into four treatment groups (group C, group L-Se, group H-fat, and group L-Se-H-fat) (n = 10/group) and fed with the corresponding diet for 16 weeks. The pig peripheral blood lymphocytes were extracted, and the mRNA expression of selenoproteins, HSPs, and cytokines was measured. Most mRNA levels for selenoproteins decreased in group L-Se, group H-fat, and group L-Se-H-fat, except Gpx1, Gpx2, Selt, and Selm, which were elevated in group H-fat. At the same time, low-Se/high-fat diet increased the expression of HSPs (HSP40, HSP60, HSP70, and HSP90) and inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-8, IL-9, iNOS, COX-2, NF-κB, and TNF-α) in group L-Se, group H-fat, and group L-Se-H-fat, and genes in group L-Se-H-fat showed greater increases. Also, low-Se/high-fat diet inhibits the expression of TGF-ß1 and IFN-γ. In summary, a low-Se/high-fat diet can cause relevant selenoprotein expression changes and promote the expression of pro-inflammatory factors and HSPs, and low Se enhances the expression of HSPs and inflammation factors induced by high fat. This information is helpful for understanding the effects of low-Se and high-fat diet on pig peripheral blood lymphocytes.

Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity.Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice.Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes.Results: Dietary selenium deficiency decreased (P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P < 0.05) mRNA levels of 1, 5, and 13 selenoproteins in the heart, kidney, and liver of males, respectively, and 6, 5, and 0 selenoproteins, respectively, in females. Among these mRNAs, selenoprotein H (Selenoh), selenoprotein M (Selenom), selenoprotein W (Selenow), methionine-R-sulfoxide reductase 1 (MsrB1), Gpx1, Gpx3, thioredoxin reductase 1 (Txnrd1), Txnrd2, selenoprotein S (Selenos), selenoprotein F (Selenof), and selenoprotein O (Selenoo) responded in parallel to dietary selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 (Dio2) and selenoprotein N (Selenon) in the kidneys of males. Age upregulated (11-44%; P < 0.05) Selenon in the kidneys of males, selenoprotein K (Selenok) and selenoprotein I (Selenoi) in the kidneys of females, and Selenof and Selenok in the testes.Conclusions: These results illustrate tissue-specific sexual dimorphisms of selenium status and selenotranscriptomes because of dietary selenium deficiency and age.

Selenium, selenoproteins and selenometabolites in mothers and babies at the time of birth.

The deficiency of Se, an essential micronutrient, has been implicated in adverse pregnancy outcomes. Our study was designed to determine total serum Se, selenoproteins (extracellular glutathione peroxidase (GPx-3), selenoprotein P (SeP)), selenoalbumin (SeAlb) and selenometabolites in healthy women and their newborns at delivery. This cross-sectional study included eighty-three healthy mother-baby couples. Total Se and Se species concentrations were measured in maternal and umbilical cord sera by an in-series coupling of two-dimensional size-exclusion and affinity HPLC. Additional measurements of serum SeP concentration and of serum GPx-3 enzyme activity were carried out using ELISA. Total Se concentration was significantly higher in maternal serum than in cord serum (68·9 (sd 15·2) and 56·1 (sd 14·6) µg/l, respectively; P<0·01). There were significant correlations between selenoprotein and SeAlb concentrations in mothers and newborns, although they also showed significant differences in GPx-3 (11·2 (sd 3·7) v. 10·5 (sd 3·5) µg/l; P<0·01), SeP (42·5 (sd 9·5) v. 28·1 (sd 7·7) µg/l; P<0·01) and SeAlb (11·6 (sd 3·6) v. 14·1 (sd 4·3) µg/l; P<0·01) concentrations in maternal and cord sera, respectively. Serum GPx-3 activity and concentration were positively correlated in mothers (r 0·33; P=0·038) but not in newborns. GPx-3 activity in cord serum was significantly correlated with gestational age (r 0·44; P=0·009). SeAlb concentration was significantly higher in babies, whereas SeP and GPx-3 concentrations were significantly higher in mothers. The differences cannot be explained by simple diffusion; specific transfer mechanisms are probably involved. GPx-3 concentrations in mothers, at delivery, are related to maternal Se status, whereas the GPx-3 activity in cord serum depends on gestational age.

Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils.

Lead (Pb) is one of the most highly toxic metal pollutant that can cause damage to the immune system. It is known that selenium (Se) can antagonize heavy metals. To explore the toxic effects of Pb poisoning on bird immune cells, as well as the alleviating effects of Se on Pb, Se supplement and/or Pb poisoning chicken models were established. One hundred and eighty Hyline 7-day-old male chickens received either Se (1mg Se per kg of diet), Pb (350mg Pb per liter water) or Se+Pb in their diet and water for 90 days. Then, whole blood was collected from the four groups of chickens, and serum and neutrophils were isolated. The levels of Se and Pb in chicken serum, mRNA levels of 24 selenoproteins (GPX1, GPX2, GPX3, GPX4, Dio1, Dio2, Dio3, Txnrd1, Txnrd2, Txnrd3, SELS, SPS2, SELK, SELW1, SEP15, SEPX1, SELT, SELI, SELO, SELM, SEPN1, SEPP1, SELU, SELH) and inflammatory factors (TNF-α, COX-2, iNOS, NF-κB), and iNOS protein level in chicken neutrophils were determined, and protein-protein interaction prediction and principal component analysis were performed. The data showed that Pb exposure increased Pb content in serum, activated the NF-κB pathway, and increased the expression of selenoproteins in chicken neutrophils. Se supplements could reduce Pb concentration in serum, had a mitigative effect on the activation of the NF-κB pathway and further enhanced the upward trend of selenoprotein expression induced by Pb exposure. These results suggest that Se supplement could eliminate Pb in serum and alleviate the activation of the NF-κB pathway under Pb exposure by increasing the expression of selenoproteins.

Plasma levels of selenium-containing proteins in Inuit adults from Nunavik.

Selenium (Se) is highly abundant in marine foods traditionally consumed by Inuit of Nunavik (Northern Quebec, Canada) and accordingly, their Se intake is among the highest in the world. However, little is known regarding the biological implications of this high Se status in this Arctic indigenous population. We used a method combining affinity chromatography and inductively coupled plasma-mass spectrometry with quantification by post-column isotope dilution to determine total Se levels and concentrations of Se-containing proteins in archived plasma samples of Inuit adults who participated to the 2004 Nunavik Inuit Health Survey (N = 852). Amounts of mercury (Hg) associated with Se-containing proteins were also quantified. Results show that glutathione peroxidase 3 (GPx3), selenoprotein P (SelP) and selenoalbumin (SeAlb) represented respectively 25%, 52% and 23% of total plasma Se concentrations. In addition, small amounts of Hg co-eluted with each Se-containing protein and up to 50% of plasma Hg was associated to SelP. Total plasma Se concentrations (median = 139 µg L− 1; interquartile range (IQR) = 22.7 µg L− 1) were markedly lower and less variable than whole blood Se concentration (median = 261 µg L− 1, IQR = 166 µg L− 1). A non linear relation was observed between whole blood Se and plasma Se levels, with plasma Se concentrations leveling off at approximately 200 µg L− 1, whereas 16% and 3% of individuals exhibited whole blood concentrations higher than 500 µg L− 1 and 1000 µg L− 1, respectively. In contrast, a linear relationship was previously reported in communities consuming Brazil nuts which are rich Se, mainly present as selenomethionine. This suggests that a different selenocompound, possibly selenoneine, is present in the Arctic marine food chain and accumulates in the blood cellular fraction of Inuit.

Role of SEP15 Gene Polymorphisms in the Time of Progression to AIDS.

AIMS: HIV infection is a chronic disease that requires intensive treatment in its later phases, including dietary supplementation. Several studies have suggested clinical improvements in patients with high levels of selenium, linking these levels with a longer progression to AIDS. The objective of this study was to verify the association of two polymorphisms in the SEP15 gene, which encodes a selenoprotein that is responsible for the transport of selenium in cells, with the time of progression to AIDS in HIV-1-infected patients. METHODS: Blood samples were obtained from 139 HIV-1-positive individuals after they provided informed consent. DNA was isolated and genotyped using real-time polymerase chain reaction for the presence of SEP15 single nucleotide polymorphisms (rs5859 and rs561104). Questionnaires on sociodemographic features and behavior were answered, and the time of progression to AIDS was estimated based on a medical chart analysis. RESULTS: The allelic and genotypic frequencies did not differ between rapid and nonrapid progressors; however, the presence of the AA genotype of the rs5859 polymorphism was associated with a shorter time of progression to AIDS compared with GG homozygotes (hazard ratio = 3.62, 95% CI = 1.55-8.43, p = 0.003). CONCLUSION: These findings show the importance of genetic analysis of the SEP15 gene in individual patients with regard to predicting time of progression to AIDS.

Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis.

Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2'-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.

DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism.

PURPOSE: Selenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status. METHODS: The trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout. RESULTS: After genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout. CONCLUSIONS: These results point to an unclear relationship between selenium, genotype, and DNA damage.