Selenium participates in the formation of kidney stones by alleviating endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells.

Objectives: To investigate the role of selenium and selenium-containing proteins in the etiology and pathogenesis of kidney stones.Methods: The HK-2 cell line was subjected to supersaturation oxalate treatment to establish an in vitro model of calcium oxalate kidney stones, while SD rats were administered with ethylene glycol to establish an in vivo model of calcium oxalate kidney stones. qPCR analysis was employed to investigate the alterations in selenoproteins within the models, and subsequently, genes exhibiting significant changes were identified. Subsequently, based on the functions of these genes, their regulatory effects on endoplasmic reticulum stress (ERS) and apoptosis during the disease progression were examined both in HK-2 cells and rat kidneys. Finally, Selenomethionine (SeMet) supplementation was introduced to explore its therapeutic potential for kidney stone management.Results: The involvement of Selenoprotein K in the pathogenesis of calcium oxalate kidney stone disease has been confirmed, exhibiting significant alterations. Manipulation of its expression levels through overexpression and knockdown techniques resulted in a corresponding reduction or increase in oxidative stress, ERS, and apoptosis within renal tubular epithelial cells. SelK regulates ERS and apoptosis by controlling the IRE1-ASK1-JNK pathway. In addition, SeMet treatment, which contains selenium, effectively reduced the levels of oxidative stress, ERS, and apoptosis in vivo and in vitro models, thereby alleviating tubular epithelial cell damage and reducing the formation of kidney stones in experimental rats.Discussion: Selenium is involved in the occurrence and development of kidney stones by regulating oxidative damage to renal tubular epithelial cells. The results suggest that dietary selenium supplementation in daily life may be of great significance for the prevention and treatment of kidney stones.

Overcoming Challenges with Biochemical Studies of Selenocysteine and Selenoproteins.

Selenocysteine (Sec) is an essential amino acid that distinguishes itself from cysteine by a selenium atom in place of a sulfur atom. This single change imparts distinct chemical properties to Sec which are crucial for selenoprotein (Sec-containing protein) function. These properties include a lower pKa, enhanced nucleophilicity, and reversible oxidation. However, studying Sec incorporation in proteins is a complex process. While we find Sec in all domains of life, each domain has distinct translation mechanisms. These mechanisms are unique to canonical translation and are composed of Sec-specific enzymes and an mRNA hairpin to drive recoding of the UGA stop codon with Sec. In this review, we highlight the obstacles that arise when investigating Sec insertion, and the role that Sec has in proteins. We discuss the strategic methods implemented in this field to address these challenges. Though the Sec translation system is complex, a remarkable amount of information has been obtained and specialized tools have been developed. Continued studies in this area will provide a deeper understanding on the role of Sec in the context of proteins, and the necessity that we have for maintaining this complex translation machinery to make selenoproteins.

Multi-therapeutic-activity selenium nanodot toward preventing brain injury and restoring neurobehavioral functions following hemorrhagic stroke.

Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases.

Effect of Selenium and Selenoproteins on Radiation Resistance.

With the advancement of radiological medicine and nuclear industry technology, radiation is increasingly used to diagnose human health disorders. However, large-scale nuclear leakage has heightened concerns about the impact on human organs and tissues. Selenium is an essential trace element that functions in the body mainly in the form of selenoproteins. Selenium and selenoproteins can protect against radiation by stimulating antioxidant actions, DNA repair functions, and immune enhancement. While studies on reducing radiation through antioxidants have been conducted for many years, the underlying mechanisms of selenium and selenoproteins as significant antioxidants in radiation damage mitigation remain incompletely understood. Therefore, this paper aims to provide new insights into developing safe and effective radiation protection agents by summarizing the anti-radiation mechanism of selenium and selenoproteins.

Selenoprotein S maintains intestinal homeostasis in ulcerative colitis by inhibiting necroptosis of colonic epithelial cells through modulation of macrophage polarization.

Rationale: Macrophage polarization plays an important role in the inflammatory regulation of ulcerative colitis (UC). In this context, necroptosis is a type of cell death that regulates intestinal inflammation, and selenoprotein S (SelS) is a selenoprotein expressed in intestinal epithelial cells and macrophages that prevents intestinal inflammation. However, the underlying mechanisms of SelS in both cell types in regulating UC inflammatory responses remain unclear. Therefore, the direct effect of SelS deficiency on necroptosis in colonic epithelial cells (CECs) was investigated. In addition, whether SelS knockdown exacerbated intestinal inflammation by modulating macrophage polarization to promote necroptosis in CECs was assessed. Methods: The UC model of SelS knockdown mice was established with 3.5% sodium dextran sulfate, and clinical indicators and colon injury were evaluated in the mice. Moreover, SelS knockdown macrophages and CECs cultured alone/cocultured were treated with IL-1ß. The M1/M2 polarization, NF-κB/NLRP3 signaling pathway, oxidative stress, necroptosis, inflammatory cytokine, and tight junction indicators were analyzed. In addition, co-immunoprecipitation, liquid chromatography-mass spectrometry, laser confocal analysis, and molecular docking were performed to identify the interacting proteins of SelS. The GEO database was used to assess the correlation of SelS and its target proteins with macrophage polarization. The intervention effect of four selenium supplements on UC was also explored. Results: Ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52) was identified as a potential interacting protein of SelS and SelS, Uba52, and yes-associated protein (YAP) was associated with macrophage polarization in the colon tissue of patients with UC. SelS deficiency in CECs directly induced reactive oxygen species (ROS) production, necroptosis, cytokine release, and tight junction disruption. SelS deficiency in macrophages inhibited YAP ubiquitination degradation by targeting Uba52, promoted M1 polarization, and activated the NF-κB/NLRP3 signaling pathway, thereby exacerbating ROS-triggered cascade damage in CECs. Finally, exogenous selenium supplementation could effectively alleviate colon injury in UC. Conclusion: SelS is required for maintaining intestinal homeostasis and that its deletion enhances necroptosis in CECs, which is further exacerbated by promoting M1 macrophage polarization, and triggers more severe barrier dysfunction and inflammatory responses in UC.

Alleviation of Lipid Disorder and Liver Damage in High-Fat Diet-Induced Obese Mice by Selenium-Enriched Cardamine violifolia with Cadmium Accumulation.

BACKGROUND/OBJECTIVES: As a hyperaccumulator of selenium (Se), Cardamine violifolia (Cv) and its peptide extract could ameliorate the negative effects of a high-fat diet (HFD). However, the effects of the coaccumulation of cadmium (Cd) in Se-enriched Cv (Cv2) and the potential confounding effect on the roles of enriched Se remain unknown. We aimed to investigate whether Cv2 could alleviate HFD-induced lipid disorder and liver damage. METHODS: Three groups of 31-week-old female mice were fed for 41 weeks (n = 10-12) with a control Cv-supplemented diet (Cv1D, 0.15 mg Se/kg, 30 µg Cd/kg, and 10% fat calories), a control Cv-supplemented HFD (Cv1HFD, 45% fat calories), and a Cv2-supplemented HFD (Cv2HFD, 1.5 mg Se/kg, 0.29 mg Cd/kg, and 45% fat calories). Liver and serum were collected to determine the element concentrations, markers of liver injury and lipid disorder, and mRNA and/or protein expression of lipid metabolism factors, heavy metal detoxification factors, and selenoproteins. RESULTS: Both Cv1HFD and Cv2HFD induced obesity, and Cv2HFD downregulated Selenoi and upregulated Dio3 compared with Cv1D. When comparing Cv2HFD against Cv1HFD, Cv2 increased the liver Se and Cd, the protein abundance of Selenoh, and the mRNA abundance of 10 selenoproteins; reduced the serum TG, TC, and AST; reduced the liver TG, lipid droplets, malondialdehyde, and mRNA abundance of Mtf1 and Mt2; and differentially regulated the mRNA levels of lipid metabolism factors. CONCLUSIONS: Cv2 alleviated HFD-induced lipid dysregulation and liver damage, which was probably associated with its unique Se speciation. However, further research is needed to explore the interaction of plant-coenriched Se and Cd and its effects on health.

An Examination of Chemical Tools for Hydrogen Selenide Donation and Detection.

Hydrogen selenide (H2Se) is an emerging biomolecule of interest with similar properties to that of other gaseous signaling molecules (i.e., gasotransmitters that include nitric oxide, carbon monoxide, and hydrogen sulfide). H2Se is enzymatically generated in humans where it serves as a key metabolic intermediate in the production of selenoproteins and other selenium-containing biomolecules. However, beyond its participation in biosynthetic pathways, its involvement in cellular signaling or other biological mechanisms remains unclear. To uncover its true biological significance, H2Se-specific chemical tools capable of functioning under physiological conditions are required but lacking in comparison to those that exist for other gasotransmitters. Recently, researchers have begun to fill this unmet need by developing new H2Se-releasing compounds, along with pioneering methods for selenide detection and quantification. In combination, the chemical tools highlighted in this review have the potential to spark groundbreaking explorations into the chemical biology of H2Se, which may lead to its branding as the fourth official gasotransmitter.

Insights into the interaction between UGGT, the gatekeeper of folding in the ER, and its partner, the selenoprotein SEP15.

The enzyme UDP-glucose: glycoprotein glucosyltransferase (UGGT) is the gatekeeper of protein folding within the endoplasmic reticulum (ER). One-third of the human proteome traverses the ER where folding and maturation are facilitated by a complex protein homeostasis network. Both glycan modifications and disulfide bonds are of key importance in the maturation of these ER proteins. The actions of UGGT are intimately linked to the glycan code for folding and maturation of secretory proteins in the ER. UGGT selectively glucosylates the N-linked glycan of misfolded proteins so that they can reenter the lectin-folding chaperone cycle and be retained within the ER for further attempts at folding. An intriguing aspect of UGGT function is its interaction with its poorly understood cochaperone, the 15 kDa selenoprotein known as SELENOF or SEP15. This small protein contains a rare selenocysteine residue proposed to act as an oxidoreductase toward UGGT substrates. AlphaFold2 predictions of the UGGT1/SEP15 complex provide insight into this complex at a structural level. The predicted UGGT1/SEP15 interaction interface was validated by mutagenesis and coimmunoprecipitation experiments. These results serve as a springboard for models of the integrated action of UGGT1 and SEP15.

Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.

Background: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking. Objective: The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care. Methods: In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction. Results: 21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients. Conclusion: ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.

SelK promotes glioblastoma cell proliferation by inhibiting ß-TrCP1 mediated ubiquitin-dependent degradation of CDK4.

BACKGROUND: Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. METHODS: Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. RESULTS: SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of ß-TrCP1 expression. Up-regulation of ß-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. CONCLUSION: This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/ß-TrCP1/CDK4 axis.

Clostridioides difficile exploits xanthine and uric acid as nutrients by utilizing a selenium-dependent catabolic pathway.

Selenium is a trace element that plays critical roles in redox biology; it is typically incorporated into "selenoproteins" as the 21st amino acid selenocysteine. Additionally, selenium exists as a labile non-selenocysteine cofactor in a small subset of selenoproteins known as selenium-dependent molybdenum hydroxylases (SDMHs). In purinolytic clostridia, SDMHs are implicated in the degradation of hypoxanthine, xanthine, and uric acid for carbon and nitrogen. While SDMHs have been biochemically analyzed, the genes responsible for the insertion and maturation of the selenium cofactor lack characterization. In this study, we utilized the nosocomial pathogen Clostridioides difficile as a genetic model to begin characterizing this poorly understood selenium utilization pathway and its role in the catabolism of host-derived purines. We first observed that C. difficile could utilize hypoxanthine, xanthine, or uric acid to overcome a growth defect in a minimal medium devoid of glycine and threonine. However, strains lacking selenophosphate synthetase (selD mutants) still grew poorly in the presence of xanthine and uric acid, suggesting a selenium-dependent purinolytic process. Previous computational studies have identified yqeB and yqeC as potential candidates for cofactor maturation, so we subsequently deleted each gene using CRISPR-Cas9 technology. We surprisingly found that the growth of the ΔyqeB mutant in response to each purine was similar to the behavior of the selD mutants, while the ΔyqeC mutant exhibited no obvious phenotype. Our results suggest an important role for YqeB in selenium-dependent purine catabolism and also showcase C. difficile as an appropriate model organism to study the biological use of selenium.IMPORTANCEThe apparent modification of bacterial molybdenum hydroxylases with a catalytically essential selenium cofactor is the least understood mechanism of selenium incorporation. Selenium-dependent molybdenum hydroxylases play an important role in scavenging carbon and nitrogen from purines for purinolytic clostridia. Here, we used Clostridioides difficile as a genetic platform to begin dissecting the selenium cofactor trait and found genetic evidence for a selenium-dependent purinolytic pathway. The absence of selD or yqeB-a predicted genetic marker for the selenium cofactor trait-resulted in impaired growth on xanthine and uric acid, known substrates for selenium-dependent molybdenum hydroxylases. Our findings provide a genetic foundation for future research of this pathway and suggest a novel metabolic strategy for C. difficile to scavenge host-derived purines from the gut.

Utilizing Thermal Shift Assay to Probe Substrate Binding to Selenoprotein O.

Defining the biological importance of proteins with unknown functions poses a significant obstacle in understanding cellular processes. Although bioinformatic and structural predictions have contributed to the study of unknown proteins, in vitro experimental validations are often hampered by the optimal conditions and cofactors required for biochemical activity. Cofactor binding is not only essential for the activity of some enzymes but may also enhance the thermal stability of the protein. One practical application of this phenomenon lies in utilizing the change in thermal stability, as measured by alterations in the protein's melting temperature, to probe ligand binding. Thermal shift assay (TSA) can be used to analyze the binding of different ligands to the protein of interest or find a stabilizing condition to perform experiments such as X-ray crystallography. Here we will describe a protocol for TSA utilizing the pseudokinase, Selenoprotein O (SelO), for a simple and high-throughput method for testing metal and nucleotide binding. In contrast to canonical kinases, SelO binds ATP in an inverted orientation to catalyze the transfer of AMP to the hydroxyl side chains of proteins in a posttranslational modification known as protein AMPylation. By leveraging the shift in the melting temperatures, we provide crucial insights into the molecular interactions underlying SelO function.

Diagnostic value of selenoprotein changes in renal tissues for acute rejection of kidney transplantation as revealed by transcriptomics.

BACKGROUND: There seems to be a close link between the changing levels of selenoproteins, which are important for maintaining redox homeostasis in the body, and acute rejection of kidney transplants. The aim of this study was to explore the diagnostic value of selenoprotein change characteristics in renal tissues for acute rejection of kidney transplantation. METHODS: We first explored the potential biological functions of 25 selenoproteins in the human body by enrichment analysis and used the HPA database to clarify the expression levels of selenoproteins in kidney tissues; We then constructed a diagnostic model using "Logistic regression analysis" and "Nomogram model"; Calibration curves and ROC curves were used to evaluate the diagnostic models, and clinical decision curves (DCA) were used to assess the diagnostic value of selenoprotein changes to the clinic; Single-gene GSEA enrichment analysis to further explore the potential regulatory mechanisms of selenoproteins; The Cibersort algorithm explores the level of immune cell infiltration and uses correlation analysis to clarify the correlation between selenoproteins and immune cells; We further assessed the diagnostic value of selenoproteins in kidney transplantation ABMR and TCMR, respectively. Finally, we validated the expression level of selenoproteins in kidney tissues by constructing a rat model of acute rejection of kidney transplantation using transcriptome sequencing. RESULTS: Our enrichment analysis revealed that selenoproteins are mainly closely associated with biological functions such as oxidative stress, inflammation, and immune regulation (P<0.05); The HPA database suggests that a total of 23 selenoproteins can be expressed in kidney tissue. We constructed a diagnostic model using these 23 selenoproteins, and both calibration curves and ROC curves proved that their change levels have good diagnostic value for acute rejection of kidney transplantation, and DCA curves proved the role of selenoproteins in clinical decision-making; Single-gene GSEA enrichment analysis revealed that selenoproteins are closely associated with immune regulation-related pathways (P<0.05); The Cibersort algorithm identified 10 immune cell infiltration levels that were significantly altered during acute rejection of kidney transplantation (P<0.05), while correlation analyses indicated that selenoproteins correlate with multiple immune cell infiltrations; In ABMR and TCMR, we again verified the diagnostic value of selenoprotein changes in acute rejection of kidney transplantation. Finally, we found significant differences in the expression levels of nine selenoproteins in a rat model of acute rejection of kidney transplantation (P<0.05). CONCLUSION: Changes in selenoproteins in renal tissues have good diagnostic value for acute rejection of kidneyl transplantation, and selenoproteins may be able to be a potential target for alleviating acute rejection of kidney transplantation.

Molecular Mechanisms of the Therapeutic Effect of Selenium Nanoparticles in Hepatocellular Carcinoma.

This review describes and summarizes, for the first time, the molecular mechanisms of the cytotoxic effect of selenium nanoparticles of various origins on hepatocellular carcinoma cells. The text provides information from recent years indicating the regulation of various signaling pathways and endoplasmic reticulum stress by selenium nanoparticles; the pathways of cell death of liver cancer cells as a result of exposure to selenium nanoparticles are considered. Particular attention is paid to the participation of selenoproteins and selenium-containing thioredoxin reductases and glutathione peroxidases in these processes. Previously, there were no reviews that fully reflected the cytotoxic effects of selenium nanoparticles specifically in hepatocellular carcinoma, despite the fact that many reviews and experimental articles have been devoted to the causes of this disease and the molecular mechanisms of regulation of cytotoxic effects by other agents. The relevance of this review is primarily explained by the fact that despite the development of various drugs and approaches for the treatment and prevention of hepatocellular carcinoma, this disease is still the fourth leading cause of death in the world. For this reason, a complete understanding of the latest trends in the treatment of oncology of various etiologies, especially hepatocellular carcinoma, is extremely important.

Selenium Discrepancies in Fetal Bovine Serum: Impact on Cellular Selenoprotein Expression.

Selenium is an essential trace element in our diet, crucial for the composition of human selenoproteins, which include 25 genes such as glutathione peroxidases and thioredoxin reductases. The regulation of the selenoproteome primarily hinges on the bioavailability of selenium, either from dietary sources or cell culture media. This selenium-dependent control follows a specific hierarchy, with "housekeeping" selenoproteins maintaining constant expression while "stress-regulated" counterparts respond to selenium level fluctuations. This study investigates the variability in fetal bovine serum (FBS) selenium concentrations among commercial batches and its effects on the expression of specific stress-related cellular selenoproteins. Despite the limitations of our study, which exclusively used HEK293 cells and focused on a subset of selenoproteins, our findings highlight the substantial impact of serum selenium levels on selenoprotein expression, particularly for GPX1 and GPX4. The luciferase reporter assay emerged as a sensitive and precise method for evaluating selenium levels in cell culture environments. While not exhaustive, this analysis provides valuable insights into selenium-mediated selenoprotein regulation, emphasizing the importance of serum composition in cellular responses and offering guidance for researchers in the selenoprotein field.

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.

New horizons for the role of selenium on cognitive function: advances and challenges.

Cognitive deficits associated with oxidative stress and the dysfunction of the central nervous system are present in some neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Selenium (Se), an essential microelement, exhibits cognition-associated functions through selenoproteins mainly owing to its antioxidant property. Due to the disproportionate distribution of Se in the soil, the amount of Se varies greatly in various foods, resulting in a large proportion of people with Se deficiency worldwide. Numerous cell and animal experiments demonstrate Se deficiency-induced cognitive deficits and Se supplementation-improved cognitive performances. However, human studies yield inconsistent results and the mechanism of Se in cognition still remains elusive, which hinder the further exploration of Se in human cognition. To address the urgent issue, the review summarizes Se-contained foods (plant-based foods, animal-based foods, and Se supplements), brain selenoproteins, mechanisms of Se in cognition (improvement of synaptic plasticity, regulation of Zn2+ level, inhibition of ferroptosis, modulation of autophagy and de novo synthesis of L-serine), and effects of Se on cognitive deficits, as well as consequently sheds light on great potentials of Se in the prevention and treatment of cognitive deficits.

Biochemical characterization, biosynthesis mechanism, and functional evaluation of selenium-enriched Aspergillus oryzae A02.

The synthesis mechanisms and function evaluation of selenium(Se)-enriched microorganism remain relatively unexplored. This study unveils that total Se content within A. oryzae A02 mycelium soared to an impressive 8462 mg/kg DCW, surpassing Se-enriched yeast by 2-3 times. Selenium exists in two predominant forms within A. oryzae A02: selenoproteins (SeMet 32.1 %, SeCys 14.4 %) and selenium nanoparticles (SeNPs; 53.5 %). The extensive quantitative characterization of the elemental composition, surface morphology, and size of SeNPs on A. oryzae A02 mycelium significantly differs from those reported for other microorganisms. Comparative RNA-Seq analysis revealed the upregulation of functional genes implicated in selenium transformation, activating multiple potential pathways for selenium reduction. The assimilatory and dissimilatory reductions of Se oxyanions engaged numerous parallel and interconnected pathways, manifesting a harmonious equilibrium in overall Se biotransformation in A. oryzae A02. Furthermore, selenium-enriched A. oryzae A02 was observed to primarily upregulate peroxisome activity while downregulating estrogen 2-hydroxylase activity in mice hepatocytes, suggesting its potential in fortifying antioxidant physiological functions and upholding metabolic balance.

Enzymatic strategies for selenium incorporation into biological molecules.

The trace element selenium (Se) is essential to the physiology of most organisms on the planet. The most well documented of Se's biological forms are selenoproteins, where selenocysteine often serves as the catalytic center for crucial redox processes. Se is also found in several other classes of biological molecules, including nucleic acids, sugars, and modified amino acids, although its role in the function of these metabolites is less understood. Despite its prevalence, only a small number of Se-specific biosynthetic pathways have been discovered. Around half of these were first characterized in the past three years, suggesting that the selenometabolome may be more diverse than previously appreciated. Here, we review the recent advances in our understanding of this intriguing biochemical space, and discuss prospects for future discovery efforts.

Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.