[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

Asgard archaeal selenoproteome reveals a roadmap for the archaea-to-eukaryote transition of selenocysteine incorporation machinery.

Selenocysteine (Sec) is encoded by the UGA codon that normally functions as a stop signal and is specifically incorporated into selenoproteins via a unique recoding mechanism. The translational recoding of UGA as Sec is directed by an unusual RNA structure, the SECIS element. Although archaea and eukaryotes adopt similar Sec encoding machinery, the SECIS elements have no similarities to each other with regard to sequence and structure. We analyzed >400 Asgard archaeal genomes to examine the occurrence of both Sec encoding system and selenoproteins in this archaeal superphylum, the closest prokaryotic relatives of eukaryotes. A comprehensive map of Sec utilization trait has been generated, providing the most detailed understanding of the use of this nonstandard amino acid in Asgard archaea so far. By characterizing the selenoproteomes of all organisms, several selenoprotein-rich phyla and species were identified. Most Asgard archaeal selenoprotein genes possess eukaryotic SECIS-like structures with varying degrees of diversity. Moreover, euryarchaeal SECIS elements might originate from Asgard archaeal SECIS elements via lateral gene transfer, indicating a complex and dynamic scenario of the evolution of SECIS element within archaea. Finally, a roadmap for the transition of eukaryotic SECIS elements from archaea was proposed, and selenophosphate synthetase may serve as a potential intermediate for the generation of ancestral eukaryotic SECIS element. Our results offer new insights into a deeper understanding of the evolution of Sec insertion machinery.

Hepatocyte-specific Selenoi deficiency predisposes mice to hepatic steatosis and obesity.

Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.

Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Endoplasmic reticulum-resident selenoproteins and their roles in glucose and lipid metabolic disorders.

Glucose and lipid metabolic disorders (GLMDs), such as diabetes, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, are significant public health issues that negatively impact human health. The endoplasmic reticulum (ER) plays a crucial role at the cellular level for lipid and sterol biosynthesis, intracellular calcium storage, and protein post-translational modifications. Imbalance and dysfunction of the ER can affect glucose and lipid metabolism. As an essential trace element, selenium contributes to various human physiological functions mainly through 25 types of selenoproteins (SELENOs). At least 10 SELENOs, with experimental and/or computational evidence, are predominantly found on the ER membrane or within its lumen. Two iodothyronine deiodinases (DIOs), DIO1 and DIO2, regulate the thyroid hormone deiodination in the thyroid and some external thyroid tissues, influencing glucose and lipid metabolism. Most of the other eight members maintain redox homeostasis in the ER. Especially, SELENOF, SELENOM, and SELENOS are involved in unfolded protein responses; SELENOI catalyzes phosphatidylethanolamine synthesis; SELENOK, SELENON, and SELENOT participate in calcium homeostasis regulation; and the biological significance of thioredoxin reductase 3 in the ER remains unexplored despite its established function in the thioredoxin system. This review examines recent research advances regarding ER SELENOs in GLMDs and aims to provide insights on ER-related pathology through SELENOs regulation.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Selenoprotein T, a potential treatment of attention-deficit/hyperactivity disorder and comorbid pain in neonatal 6-OHDA lesioned mice.

pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain. Growing evidence suggests that oxidative stress may be crucial in both pathologies. Recent studies revealed that a small peptide encompassing the redox-active site of selenoprotein T (PSELT), protects dopaminergic neurons and fibers as well as lesioned nerves in animal models. The current study aims to examine the effects of PSELT treatment on ADHD-like symptoms and pain sensitivity, as well as the role of catecholaminergic systems in these effects. Our results demonstrated that intranasal administration of PSELT reduced the hyperactivity in the open field, decreased the impulsivity displayed by 6-OHDA-lesioned male mice in the 5-choice serial reaction time task test and improved attentional performance. In addition, PSELT treatment significantly increased the nociception threshold in both normal and inflammatory conditions. Furthermore, anti-hyperalgesic activity was antagonized with sulpiride pre-treatment, but not by phentolamine, or propranolol pre-treatments. The present study suggests that PSELT reduces the severity of ADHD symptoms in mice and possesses potent antinociceptive effects which could be related to the involvement of D2/D3 dopaminergic receptors.

Relationship between Serum Concentrations and Muscular Expressions of Selenoproteins on Selenium-Supplemented Insulin Resistance Mouse Model.

Previously, insulin resistance and hepatic oxidative stress with increased expressions of glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were induced in NSY mice, a diabetic mouse model, by administrating a high fat diet (HFD) and seleno-L-methionine (SeMet) for 12 weeks. In this study we developed an analysis method for serum selenoproteins using LC-tandem mass spectrometry (LC-MS/MS) and investigated the effects of supplementary selenium on serum concentrations of selenoproteins as well as protein expression in skeletal muscle as a major insulin target tissue under the same experimental condition. The glucose area under the curves for oral glucose tolerance and insulin tolerance tests indicated that the HFD induced insulin resistance, whereas the treatment of SeMet + HFD showed insignificant promotion compared with the HFD-induced insulin resistance. Although the expressions of GPx1 in gastrocnemius and soleus were not significantly induced by supplementary SeMet nor HFD administration, the expressions of SelP in both skeletal muscles were significantly induced by the treatment of SeMet + HFD. There were also significant increases in serum concentrations of SelP by supplementary SeMet + HFD administration, whereas GPx3 was augmented by supplementary SeMet only. These results indicated that the HFD intake under the sufficient selenium status augmented the blood secretion of SelP, which may participate in the reduction of insulin sensitivity in skeletal muscles as well as liver or adipose tissues, and it is a better indicator of deterioration than GPx3 as it is a major selenoprotein in serum.

Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species emerges as a viable approach to addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly lentinan-Se (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of osteoclastogenesis. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over osteoclastogenesis inhibition, and the prevention of osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders.

Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination.

Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.

Proteomic and transcriptomic analysis of selenium utilization in Methanococcus maripaludis.

Methanococcus maripaludis utilizes selenocysteine- (Sec-) containing proteins (selenoproteins), mostly active in the organism's primary energy metabolism, methanogenesis. During selenium depletion, M. maripaludis employs a set of enzymes containing cysteine (Cys) instead of Sec. The genes coding for these Sec-/Cys-containing isoforms were the only genes known of which expression is influenced by the selenium status of the cell. Using proteomics and transcriptomics, approx. 7% and 12%, respectively, of all genes/proteins were found differentially expressed/synthesized in response to the selenium supply. Some of the genes identified involve methanogenesis, nitrogenase functions, and putative transporters. An increase of transcript abundance for putative transporters under selenium depletion indicated the organism's effort to tap into alternative sources of selenium. M. maripaludis is known to utilize selenite and dimethylselenide as selenium sources. To expand this list, a selenium-responsive reporter strain was assessed with nine other, environmentally relevant selenium species. While the effect of some was very similar to that of selenite, others were effectively utilized at lower concentrations. Conversely, selenate and seleno-amino acids were only utilized at unphysiologically high concentrations and two compounds were not utilized at all. To address the role of the selenium-regulated putative transporters, M. maripaludis mutant strains lacking one or two of the putative transporters were tested for the capability to utilize the different selenium species. Of the five putative transporters analyzed by loss-of-function mutagenesis, none appeared to be absolutely required for utilizing any of the selenium species tested, indicating they have redundant and/or overlapping specificities or are not dedicated selenium transporters. IMPORTANCE: While selenium metabolism in microorganisms has been studied intensively in the past, global gene expression approaches have not been employed so far. Furthermore, the use of different selenium sources, widely environmentally interconvertible via biotic and abiotic processes, was also not extensively studied before. Methanococcus maripaludis JJ is ideally suited for such analyses, thanks to its known selenium usage and available genetic tools. Thus, an overall view on the selenium regulon of M. maripaludis was obtained via transcriptomic and proteomic analyses, which inspired further experimentation. This led to demonstrating the use of selenium sources M. maripaludis was previously not known to employ. Also, an attempt-although so far unsuccessful-was made to pinpoint potential selenium transporter genes, in order to deepen our understanding of trace element utilization in this important model organism.

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure.

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF.

Ancient Loss of Catalytic Selenocysteine Spurred Convergent Adaptation in a Mammalian Oxidoreductase.

Selenocysteine, the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Selenocysteine is analogous to the common cysteine amino acid, but its selenium atom offers physical-chemical properties not provided by the corresponding sulfur atom in cysteine. Catalytic sites with selenocysteine in selenoproteins of vertebrates are under strong purifying selection, but one enzyme, glutathione peroxidase 6 (GPX6), independently exchanged selenocysteine for cysteine <100 million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after selenocysteine was lost and up to today and found them to have lost their classic ability to reduce hydroperoxides using glutathione. This loss of function, however, was accompanied by additional amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning selenocysteine in glutathione peroxidase 6. This demonstrates a narrow evolutionary range in maintaining fitness when sulfur in cysteine impairs the catalytic activity of this protein, with pleiotropy and epistasis likely driving the observed convergent evolution. We propose that the mutations shared across distinct lineages may trigger enzymatic properties beyond those in classic glutathione peroxidases, rather than simply recovering catalytic rate. These findings are an unusual example of adaptive convergence across mammalian selenoproteins, with the evolutionary signatures possibly representing the evolution of novel oxidoreductase functions.

ER stress and ERO1: Potential therapeutic targets for inherited myopathies.

Selenoprotein N-related myopathy (SEPN1-RM) is a genetic disease that causes muscle weakness and respiratory failure. Germani et al.1 demonstrate that diaphragm weakness in SEPN1-RM is prevented by the inhibition of ER stress or ERO1 oxidoreductase regulated by transcription factor CHOP.

Research progress on the biological regulatory mechanisms of selenium on skeletal muscle in broilers.

As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong anti-inflammatory, antioxidant, and immune enhancing abilities. The biological functions of selenium are primarily driven by its presence in selenoproteins as a form of selenocysteine. Broilers are highly sensitive to selenium intake. Recent reports have demonstrated that selenium deficiency can adversely affect the quality of skeletal muscles and the economic value of broilers; the regulatory roles of several key selenoproteins (e.g., GPX1, GPX4, TXNRD1, TXNRD3, SelK, SelT, and SelW) have been identified. Starting from the selenium metabolism and its biological utilization in the skeletal muscle, the effect of the selenium antioxidant function on broiler meat quality is discussed in detail. The progress of research into the prevention of skeletal muscle injury by selenium and selenoproteins is also summarized. The findings emphasize the necessity of in vivo and in vitro research, and certain mechanism problems are identified, which aids their further examination. This mini-review will be helpful to provide a theoretical basis for the further study of regulatory mechanisms of selenium nutrition in edible poultry.

Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase due in part to the obesity epidemic and to environmental exposures to metabolism disrupting chemicals. A single gavage exposure of male mice to Aroclor 1260 (Ar1260), an environmentally relevant mixture of non-dioxin-like polychlorinated biphenyls (PCBs), resulted in steatohepatitis and altered RNA modifications in selenocysteine tRNA 34 weeks post-exposure. Unbiased approaches identified the liver proteome, selenoproteins, and levels of 25 metals. Ar1260 altered the abundance of 128 proteins. Enrichment analysis of the liver Ar1260 proteome included glutathione metabolism and translation of selenoproteins. Hepatic glutathione peroxidase 4 (GPX4) and Selenoprotein O (SELENOO) were increased and Selenoprotein F (SELENOF), Selenoprotein S (SELENOS), Selenium binding protein 2 (SELENBP2) were decreased with Ar1260 exposure. Increased copper, selenium (Se), and zinc and reduced iron levels were detected. These data demonstrate that Ar1260 exposure alters the (seleno)proteome, Se, and metals in MASLD-associated pathways.

SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aß phagocytosis.

Amyloid-beta (Aß) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aß phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aß phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aß phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aß pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.

Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines.

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.

The mechanism of selenium regulating the permeability of vascular endothelial cells through selenoprotein O.

Vascular diseases, a leading cause of death in human, are strongly associated with pathological damage to blood vessels. The selenoprotein (Sel) have been reported to play important roles in vascular disease. However, the role of SelO in vascular disease has not been conclusively investigated. The present experiment was to investigate the regulatory mechanism of the effect of SelO on the permeability of vascular endothelial. The H.E staining, FITC-Dextran staining, Dil-AC-LDL staining and FITC-WGA staining showed that vascular structure was damaged, and intercellular junctions were disrupted with selenium (Se)-deficient. Immunohistochemistry, qPCR and Western blot revealed decreased expression of the adhesion plaque proteins vinculin, talin and paxillin, decreased expression of the vascular connectivity effector molecules connexin, claudin-1 and E-cadherin and increased expression of JAM-A and N-cadherin, as well as decreased expression of the ZO-1 signaling pathways ZO-1, Rock, rhoGEF, cingulin and MLC-2. In a screening of 24 Sel present in mice, SelO showed the most pronounced changes in vascular tissues, and a possible association between SelO and vascular intercellular junction effectors was determined using IBM SPSS Statistics 25. Silencing of SelO, vascular endothelial intercellular junction adverse effects present. The regulatory relationship between SelO and vascular endothelial intercellular junctions was determined. The results showed that Se deficiency lead to increased vascular endothelial permeability and vascular tissue damage by decreasing SelO expression, suggesting a possible role for SelO in regulating vascular endothelial permeability.