Selenoprotein Expression Research Articles

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

Effects of different selenium sources and levels on the physiological state, selenoprotein expression, and production and preservation of selenium-enriched eggs in laying hens

Selenium (i.e., Se) is a trace element that is vital in poultry nutrition, and optimal forms and levels of Se are critical for poultry productivity and health. This study aimed to compare the effects of sodium selenite (SS), yeast selenium (SY), and methionine selenium (SM) at selenium levels of 0.15 mg/kg and 0.30 mg/kg on production performance, egg quality, egg selenium content, antioxidant capacity, immunity and selenoprotein expression in laying hens. The trial was conducted in a 3 × 2 factorial arrangement, and a total of 576 forty-three-wk-old Hyland Brown laying hens were randomly assigned into 6 treatment groups, with diets supplemented with 0.15 mg Se/kg and 0.3 mg Se/kg of SS, SY and SM for 8 wk, respectively. Results revealed that SM increased the laying rate compared to SS and SY (P < 0.05), whereas different selenium levels had no effect. Organic selenium improved egg quality, preservation performance, and selenium deposition compared to SS (P < 0.05), while SY and SM had different preferences for Se deposition in the yolk and albumen. Also, organic selenium enhanced the antioxidant capacity and immune functions of laying hens at 0.15 mg Se/kg, whereas no obvious improvement was observed at 0.30 mg Se/kg. Moreover, SY and SM increased the mRNA expression of most selenoproteins compared to SS (P < 0.05), with SM exhibiting a more pronounced effect. Correlation analysis revealed a strong positive association between glutathione peroxidase 2 (GPx2), thioredoxin reductases (TrxRs), selenoprotein K (SelK), selenoprotein S (SelS), and antioxidant and immune properties. In conclusion, the use of low-dose organic selenium is recommended as a more effective alternative to inorganic selenium, and a dosage of 0.15 mg Se/kg from SM is recommended based on the trail conditions.

The effect of High-intensity interval training with Portulaca oleracea Hydroalcoholic extract on gene expression of Selenoprotein P (SeP) and insulin resistance in rats with nonalcoholic fatty liver

The effect of High-intensity interval training with Portulaca oleracea Hydroalcoholic extract on gene expression of Selenoprotein P (SeP) and insulin resistance in rats with nonalcoholic fatty liver

Injectable hydrogel with selenium nanoparticles delivery for sustained glutathione peroxidase activation and enhanced osteoarthritis therapeutics

Reactive oxygen burst in articular chondrocytes is a major contributor to osteoarthritis progression. Although selenium is indispensable role in the antioxidant process, the narrow therapeutic window, delicate toxicity margins, and lack of an efficient delivery system have hindered its translation to clinical applications. Herein, transcriptomic and biochemical analyses revealed that osteoarthritis was associated with selenium metabolic abnormality. A novel injectable hydrogel to deliver selenium nanoparticles (SeNPs) was proposed to intervene selenoprotein expression for osteoarthritis treatment. The hydrogels based on oxidized hyaluronic acid (OHA) cross-linked with hyaluronic acid-adipic acid dihydrazide (HA-ADH) was formulated to load SeNPs through a Schiff base reaction. The hydrogels were further incorporated with SeNPs, which exhibited minimal toxicity, mechanical properties, self-healing capability, and sustained drug release. Encapsulated with SeNPs, the hydrogels facilitated cartilage repair through synergetic effects of scavenging reactive oxygen species (ROS) and depressing apoptosis. Mechanistically, the hydrogel restored redox homeostasis by targeting glutathione peroxidase-1 (GPX1). Therapeutic outcomes of the SeNPs-laden hydrogel were demonstrated in an osteoarthritis rat model created by destabilization of the medial meniscus, including cartilage protection, subchondral bone sclerosis improvement, inflammation attenuation, and pain relief were demonstrated. These results highlight therapeutic potential of OHA/HA-ADH@SeNPs hydrogels, providing fundamental insights into remedying selenium imbalance for osteoarthritis biomaterial development.

Comparative investigation of selenium-enriched Pleurotus ostreatus and Ganoderma lucidum as natural sources of selenium supplementation

Selenium (Se) is an essential trace element for human health, but its nutritional supply is insufficient in large parts of the world. Mushrooms can be enriched in selenium and can serve as alternative and natural source of selenium supplementation. In the present study, two common mushroom species (Pleurotus ostreatus and Ganoderma lucidum), were enriched with two selenium compounds (selenite and selenate) to test their suitability as natural sources of selenium supplementation. Sharp differences in the the metabolic patterns of the fortified selenium were observed. Selenium was effectively metabolized in P. ostreatus but remained in inorganic form in G. lucidum. However, mushrooms extracts were effective in enhancing selenoprotein expression in cell lines. The present study highlights the importance of employing selenium speciation analysis with an element-selective technique to examine the metabolic products following mushroom fortification for nutritional purposes due to the different toxicological profile and bioavailability of different selenium biotransformation products.

Spatial transcriptomic profiling and selenoprotein expression in mouse brain following glucocorticoid administration

Spatial transcriptomic profiling and selenoprotein expression in mouse brain following glucocorticoid administration

Application of Se-Met to CdTe QDs significantly reduces toxicity by modulating redox balance and inhibiting apoptosis

Cadmium tellurium quantum dots (CdTe QDs) as one of the most widely used QDs have been reported the toxicity and biosafety in recent years, little work has been done to reduce their toxicity however. Based on the mechanisms of toxicity of CdTe QDs on liver target organs such as oxidative stress and apoptosis previously reported by other researchers, we investigated the mechanism of action of trace element selenium (Se) to mitigate the hepatotoxicity of CdTe QDs. The experimental results showed that Se-Met at 40–140 μg L−1 could enhance the function of intracellular antioxidant defense system and the molecular structure of related antioxidant enzymes by reduce the production of ROS by 45%, protecting the activity of antioxidants and up-regulating the expression of selenoproteins with antioxidant functions, Gpx1 increase 225% and Gpx4 upregulated 47%. In addition, Se-Met could alleviate CdTe QDs-induced apoptosis by regulating two apoptosis-inducing factors, as intracellular caspase 3/9 expression levels were reduced by 70% and 87%, decreased Ca2+ concentration, and increased mitochondrial membrane potential measurements. Overall, this study indicates that Se-Met has a significant protective effect on the hepatotoxicity of CdTe QDs. Se-Met can be applied to the preparation of CdTe QDs to inhibit its toxicity and break the application limitation.

Different Dietary Sources of Selenium Alleviate Hepatic Lipid Metabolism Disorder of Heat-Stressed Broilers by Relieving Endoplasmic Reticulum Stress.

As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium selenite; selenium yeast; selenomethionine; nano-Se) on HS-induced hepatic lipid metabolism disorder and the corresponding response of selenotranscriptome in the liver of broilers. The results showed that HS-induced liver injury and hepatic lipid metabolism disorder, which were reflected in the increased activity of serum alanine aminotransferase (ALT), the increased concentration of triacylglycerol (TG) and total cholesterol (TC), the increased activity of acetyl-CoA carboxylase (ACC), diacylglycerol O-acyltransferase (DGAT) and fatty acid synthase (FAS), and the decreased activity of hepatic lipase (HL) in the liver. The hepatic lipid metabolism disorder was accompanied by the increased mRNA expression of lipid synthesis related-genes, the decreased expression of lipidolysis-related genes, and the increased expression of endoplasmic reticulum (ER) stress biomarkers (PERK, IRE1, ATF6, GRP78). The dietary supplementation of four Se sources exhibited similar protective effects. Four Se sources increased liver Se concentration and promoted the expression of selenotranscriptome and several key selenoproteins, enhanced liver antioxidant capacity and alleviated HS-induced ER stress, and thus resisted the hepatic lipid metabolism disorders of broilers exposed to HS. In conclusion, dietary supplementation of four Se sources (0.3 mg/kg) exhibited similar protective effects on HS-induced hepatic lipid metabolism disorders of broilers, and the protective effect is connected to the relieving of ER stress.

Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry.

Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study

IntroductionLow serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date.MethodsThis study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network – Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality.Results237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50–0.98).ConclusionsThis first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival.

Regorafenib activates oxidative stress by inhibiting SELENOS and potentiates oxaliplatin-induced cell death in colon cancer cells

Colorectal cancer (CRC) is the third most common cancer, and is one of the leading causes of cancer-related death worldwide. At the time of diagnosis, about 20% of patients with CRC present metastatic disease. Regorafenib, an oral multi-kinase inhibitor, has been demonstrated the efficacy and tolerability in patients with metastatic CRC. Oxaliplatin is a frontline treatment regimen for CRC, and combination treatments with oxaliplatin and other chemotherapeutic agents exert superior therapeutic effects. However, side effects and drug resistance limited their further clinical application. Here, we found that combined treatment with regorafenib and oxaliplatin synergistically enhanced anti-tumor activities in CRC by activating reactive oxygen species (ROS) mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 signaling pathways. Regorafenib promoted ROS production by suppressing the expression of selenoprotein S (SELENOS). Knocking down SELENOS sensitized ROS-mediated anti-tumor effects of regorafenib in CRC cells. Furthermore, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with regorafenib and oxaliplatin. This study provided solid experimental evidences for the combined treatment with regorafenib and oxaliplatin in CRC.

Selenium modulates AR/IGF-1R/EGFR and TROP2 signaling pathways and improves anticancer efficacy in murine mammary carcinoma 4T1

The micronutrient selenium (Se) has been shown to exert potential anticancer properties. This study aimed to evaluate the effects of Se (in Se yeast form) on the selenoproteins (SELENO), AR/IGF-1R/EGFR, PI3K/Akt/mTOR and Ras/Raf/ERK cascades, and immune checkpoint blockade in TNBC murine 4T1 cells. We also assessed the effects of combination treatment with chemotherapeutic doxorubicin and Se on trophoblast cell surface antigen 2 (TROP2) levels. Compared with the control groups, cells incubated with Se (0.25, 0.5, 0.75, 1.0, 1.5 µg Se/mL) have lower viability, raised intracellular Se concentrations and SELENO expression, and higher malondialdehyde products in a dose-dependent manner. Se induced the inactivation of AR/IGF-1R/EGFR and downregulation of the PI3K/Akt/mTOR and Ras/Raf/ERK signaling molecules. Se-treated cells also exhibited decreased mitochondrial membrane potential, reduced levels of the cell cycle regulatory protein cyclin D1, cancer stemness, metastatic and EMT-related markers, and increased apoptosis. Subsequently, Se treatment significantly suppressed PD-1/PD-L1 and CTLA-4 mRNA levels and proteins. Doxorubicin decreased 4T1 cell viability and TROP2 expression levels, but the addition of Se to doxorubicin contributed to further reductions. Similar responses to Se treatment were also observed in the human MDA-MB-231 and MCF-7 breast cancer cells. These results show that Se upregulates SELENO and anti-AR/IGF-1R/EGFR signaling in TNBC cells, thus inducing oxidative stress-dependent apoptosis and cell cycle arrest, stemness, EMT, and metastasis, as well as blocking the immune checkpoint molecules. TROP2 down-regulation with Se is also a potential anti-TNBC therapeutic target.

Translational Selenium Nanoparticles to Attenuate Allergic Dermatitis through Nrf2-Keap1-Driven Activation of Selenoproteins.

Easy recurrence and strong treatment side effects significantly limit the clinical treatment of allergic dermatitis. The human trace element selenium (Se) plays essential roles in redox regulation through incorporation into selenoproteins in the form of 21st necessary amino acid selenocysteine, to participates in the pathogenesis and intervention of chronic inflammatory diseases. Therefore, based on the safe and elemental properties of Se, we construct a facile-synthesis strategy for antiallergic selenium nanoparticles (LET-SeNPs), and scale up the production by employing a spray drying method with lactose (Lac-LET-SeNPs) or maltodextrin (Mal-LET-SeNPs) as encapsulation agents realizing larger scale production and a longer storage time. As expected, these as-prepared LET-SeNPs could effectively activate the Nrf2-Keap1 signaling pathway to enhance the expression of antioxidative selenoprotein at mRNA and protein levels, then inhibit mast cell activation to achieve efficient antiallergic activity. Interestingly, LET-SeNPs undergo metabolism to seleno-amino acids to promote biosynthesis of selenoproteins, which could suppress ROS-induced cyclooxygenase-2 (COX-2) and MAPKs activation to suppress the release of histamine and inflammatory cytokines. Allergic mouse and Macaca fascicularis models further confirm that LET-SeNPs could increase the Se content and selenoprotein expression in the skin, decrease mast cells activation and inflammatory cells infiltration, and finally exhibit the high therapeutic effects on allergic dermatitis. Taken together, this study not only constructs facile large-scale synthesis of translational Se nanomedicine to break through the bottleneck problem of nanomaterials but also sheds light on its application in the intervention and treatment of allergies.

Interactive influences of dietary selenium and oxidized fish oil on growth, nutritional composition, muscle development, antioxidant responses and selenoprotein expression in the muscle of yellow catfish Pelteobagrus fulvidraco

The current study is conducted to determine the influences of dietary selenium (Se) and oxidized fish oil (OFO) on growth, nutritional composition, muscle development, antioxidant responses and selenoprotein expression in the muscle of yellow catfish. We used the 2 × 2 factorial experimental design, which included two dietary Se levels at 0.25 (adequate) and 0.5 (high) mg Se/kg diets, and each Se level had fresh fish oil (FFO) and OFO, respectively. The experiment continued for 10 weeks. Compared to FFO group, dietary OFO reduced final body weight (FBW), specific growth rate (SGR) and weight gain (WG), and the contents of n-6 polyunsaturated fatty acid (PUFA), 18: 2n-6, 20: 4n-6, n-3 PUFA, 20: 5n-3, 22: 6n-3 and total PUFA, the diameters of muscle fibers >80 μm, mRNA expression of mef2d, myf5, myod, s6kb and mTOR, and the ratio of p-mTOR to mTOR protein expression, but increased feed conversion rate (FCR), muscle lipid content, malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities, the number of the muscle fiber with the diameter lower than 50 μm; high dietary Se addition alleviated OFO- induced variations of these indices mentioned above. Dietary OFO also reduced muscle catalase (CAT) and glutathione peroxidase (GPX) activities and total antioxidant capacity (AOC), and mRNA expression of gpx1, gpx2, gpx3, selenoe, selenok and selenos, but increased total superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and NRF2 protein expression, and high dietary Se addition alleviated OFO-induced changes of these parameters involved in antioxidant responses and selenoprotein expression in the muscle of yellow catfish. Based on these observations above, dietary Se addition alleviated OFO-induced lipogenesis, and reversed the OFO-induced inhibition of muscle growth and development, and oxidative damage of muscle. Our study provides new mechanistic insights into the Se and OFO interaction in fish. Statement of relevanceThe biological basis through which dietary OFO and Se diets interacted to affect muscle metabolism and physiology is scarce. Our study indicated that dietary Se could alleviate OFO-induced negative effects on muscle metabolism and physiology, which will be helpful to the feed formulation and fish farm.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination.Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6–15.6% in CFS versus 0.9–2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) μg/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3.We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce selenoprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials.

Therapeutic Effects of Selenium on Alpha-Synuclein Accumulation in Substantia Nigra Pars Compacta in a Rat Model of Parkinson's Disease: Behavioral and Biochemical Outcomes.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the accumulation of accumulated alpha-synuclein (α-Syn) in substantia nigra. Research has shown that selenium (Se) can protect neural cells through the actions of selenoproteins, including selenoprotein P (SelP) and selenoprotein S (SelS), which participate in endoplasmic reticulum-associated protein degradation (ERAD). In this study, we investigated the potential protective role of Se in a pre-clinical PD rat model.We aimed to evaluate the therapeutic effects of Se administration in the 6-hydroxydopamine (6-OHDA) induced unilateral rat PD model. Male Wistar rats were utilised for unilateral PD animal model which were subjected to stereotaxic surgery and injected with 20 μg 6-OHDA/5 μl 0.2% ascorbate saline. After confirming the model, the rats were intraperitoneally injected with 0.1, 0.2, and 0.3 mg/kg of sodium selenite for 7 days. We then performed behavioral tests, including apomorphine-induced rotation, hanging, and rotarod tests. Following sacrifice, we analysed the substantia nigra area of the brain and serum for protein quantification, element analysis, and gene expression analysis.Our results indicate that the administration of 0.3 mg/kg of Se improved the motor deficiency in hanging, rotarod, and apomorphine-induced rotational tests. While there was no significant improvement in the expression of α-Syn, Se increased the expression of selenoproteins. Additionally, levels of selenoproteins, Se, and α-Syn both brain and serum were re-established by the treatment, suggesting the role of Se on the α-Syn accumulation. Furthermore, Se improved PD-induced biochemical deficits by increasing the levels of SelS and SelP (p<0.005).In conclusion, our findings suggest that Se may have a protective role in PD. 0.3 mg/kg dosage of Se increased the expression of selenoproteins, reduced the accumulation of α-Syn in the brain, and improved PD-induced motor deficits. These results suggest that Se may be a potential therapeutic option for PD treatment.

Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress

BackgroundThe skeletal muscle of pigs is vulnerable to oxidative damage, resulting in growth retardation. Selenoproteins are important components of antioxidant systems for animals, which are generally regulated by dietary selenium (Se) level. Here, we developed the dietary oxidative stress (DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.ResultsDietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation, which is accompanied by mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and protein and lipid metabolism disorders. Supplementation with Se (0.3, 0.6 or 0.9 mg Se/kg) in form of hydroxy selenomethionine (OH-SeMet) linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins, which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle, and the mitigation of mitochondrial dysfunction and ER stress. What's more, selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle. However, several parameters such as the activity of GSH-Px and T-SOD, the protein abundance of JNK2, CLPP, SELENOS and SELENOF did not show dose-dependent changes. Notably, several key selenoproteins such as MSRB1, SELENOW, SELENOM, SELENON and SELENOS play the unique roles during this protection.ConclusionsIncreased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress, recover protein and lipid biosynthesis, thus alleviate skeletal muscle growth retardation. Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.

Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

A homozygous mutation in the human selenocysteine tRNA gene impairs UGA recoding activity and selenoproteome regulation by selenium.

The selenocysteine (Sec) tRNA (tRNA[Ser]Sec) governs Sec insertion into selenoproteins by the recoding of a UGA codon, typically used as a stop codon. A homozygous point mutation (C65G) in the human tRNA[Ser]Sec acceptor arm has been reported by two independent groups and was associated with symptoms such as thyroid dysfunction and low blood selenium levels; however, the extent of altered selenoprotein synthesis resulting from this mutation has yet to be comprehensively investigated. In this study, we used CRISPR/Cas9 technology to engineer homozygous and heterozygous mutant human cells, which we then compared with the parental cell lines. This C65G mutation affected many aspects of tRNA[Ser]Sec integrity and activity. Firstly, the expression level of tRNA[Ser]Sec was significantly reduced due to an altered recruitment of RNA polymerase III at the promoter. Secondly, selenoprotein expression was strongly altered, but, more surprisingly, it was no longer sensitive to selenium supplementation. Mass spectrometry analyses revealed a tRNA isoform with unmodified wobble nucleotide U34 in mutant cells that correlated with reduced UGA recoding activities. Overall, this study demonstrates the pleiotropic effect of a single C65G mutation on both tRNA phenotype and selenoproteome expression.

Comparison of Sodium Selenite and Selenium-Enriched Spirulina Supplementation Effects After Selenium Deficiency on Growth, Tissue Selenium Concentrations, Antioxidant Activities, and Selenoprotein Expression in Rats.

Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 μg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 μg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus.