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Poultry Science Jun 2024This study aimed to investigate how various selenium sources affect the intestinal health of broiler chickens. A total of 384, one-day-old Arbor Acres broilers were...
This study aimed to investigate how various selenium sources affect the intestinal health of broiler chickens. A total of 384, one-day-old Arbor Acres broilers were weighed and randomly allocated to four treatment groups. The control diet was a basal diet added with: 0.2 mg/kg Sodium Selenite (SS-control), 0.2 mg/kg Selenium nano-particles (Nano-Se), 0.2 mg/kg Selenomethionine (SeMet), and 0.2 mg/kg Selenocysteine (Sec) as the treatments. The results indicated that Nano-Se and SeMet were effective in enhancing the villus height (VH) and the villus height/crypt depth ratio (VH/CD) in the jejunum compared to (SS) (P < 0.05). The inclusion of Nano-Se into the diets increased the mRNA levels of zonula occluden-1 (ZO-1), ZO-2, Occludin, Claudin-1, and Claudin-3 compared to the SS diet (P < 0.05). The SeMet increased the levels of ZO-1 and Claudin-3 compared to the SS (P < 0.05). Moreover, SeMet upregulated the marker genes of intestinal enteroendocrine cells, stem cells, and epithelial cells compared to the SS diet (P < 0.05). However, supplementation of Nano-Se reduced the mRNA levels of interleukin 1β (IL-1β), and IL-8 and the concentration of reactive oxygen species (ROS) in the jejunum compared to the SS (P < 0.05). The Nano-Se and SeMet also increased the protein levels of CAT and SOD compared to the SS and Sec diet (P < 0.05). The number of the goblet cells and Mucin-2 (Muc2) levels were the highest in the Nano-Se group (P < 0.05). The protein expression levels of goblet cell differentiation regulator (v-myc avian myelocytomatosis viral oncogene homolog, c-Myc) were highest in the Nano-Se compared to the SS diet (P < 0.05). The Nano-Se decreased the mRNA and protein levels of NLRP3 signaling pathway-related genes compared to the SS diet (P < 0.05). In conclusion, our study demonstrated that Nano-Se and SeMet are better at improving the intestinal health of 21-day-old broilers. Additionally, Nano-Se demonstrated superior antioxidant and anti-inflammatory effects, promoting the development of intestinal goblet cells by modifying the NLRP3 signaling pathway.
PubMed: 38945002
DOI: 10.1016/j.psj.2024.103958 -
The ISME Journal Jun 2024Selenocysteine (Sec) is encoded by the UGA codon that normally functions as a stop signal and is specifically incorporated into selenoproteins via a unique recoding...
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 Sec insertion sequence (SECIS) element. Although archaea and eukaryotes adopt a similar Sec encoding machinery, the SECIS elements have no similarities to each other with regard to sequence and structure. We analyzed more than 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.
PubMed: 38896033
DOI: 10.1093/ismejo/wrae111 -
BioRxiv : the Preprint Server For... Jun 2024Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and has traditionally been thought to begin with the uptake of the Sec...
Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and has traditionally been thought to begin with the uptake of the Sec carrier selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP undergoes metabolisation via selenocysteine lyase (SCLY), producing selenide, a substrate used by selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor - selenophosphate - for the biosynthesis of the selenocysteine tRNA. Here, we report the discovery of an alternative pathway mediating Sec metabolisation that is independent of SCLY and mediated by peroxiredoxin 6 (PRDX6). Mechanistically, we demonstrate that PRDX6 can readily react with selenide and interact with SEPHS2, potentially acting as a selenium delivery system. Moreover, we demonstrate the presence and functional significance of this alternative route in cancer cells where we reveal a notable association between elevated expression of PRDX6 with a highly aggressive neuroblastoma subtype. Altogether, our study sheds light on a previously unrecognized aspect of Sec metabolism and its implications in ferroptosis, offering new avenues for therapeutic exploitation.
PubMed: 38895225
DOI: 10.1101/2024.06.04.597364 -
BioRxiv : the Preprint Server For... May 2024Many of the proteins that contain the amino acid selenocysteine are required for optimal defense against cellular stress. As such, one might expect selenoprotein...
BACKGROUND AND AIMS
Many of the proteins that contain the amino acid selenocysteine are required for optimal defense against cellular stress. As such, one might expect selenoprotein synthesis to persist or be induced upon cellular insult. Because selenocysteine is incorporated by a complex post-transcriptional mechanism, monitoring the transcription of selenoprotein genes is not adequate to understand the regulation of selenoprotein synthesis. We aimed to determine whether selenoprotein synthesis is regulated by the induction of hepatotoxic stress.
METHODS
We used hepatotropic clinically relevant drugs to evaluate the regulation of selenoprotein synthesis in human hepatocarcinoma cells.
RESULTS
We found that two drugs, benzbromarone and sorafenib, caused significant inhibition of selenoprotein synthesis. However, the loss of selenoprotein expression was not specific as total protein synthesis was similarly down-regulated only by benzbromarone and sorafenib.
CONCLUSIONS
These results allow us to conclude that these hepatotoxins do not induce or preserve selenoprotein synthesis as a protective mechanism.
HIGHLIGHTS
The treatment of liver cells with hepatotoxic and hepatotropic compounds does not result in increased synthesis of selenoproteins.Compounds that induced the canonical oxidative stress response that features NRF2 activation eliminated selenoprotein synthesis.The downregulation of selenoproteins was accompanied by general inhibition of protein synthesis.
PubMed: 38826422
DOI: 10.1101/2023.05.12.540527 -
Plant Cell Reports May 2024Identification of selenium stress-responsive expression and molecular docking of serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) in Cardamine...
Identification of selenium stress-responsive expression and molecular docking of serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) in Cardamine hupingshanensis. A complex coupled with serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) is the key enzyme that catalyzes selenocysteine (Sec) synthesis in plants. The functions of SAT and OASTL genes were identified in some plants, but it is still unclear whether SAT and OASTL are involved in the selenium metabolic pathway in Cardamine hupingshanensis. In this study, genome-wide identification and comparative analysis of ChSATs and ChOASTLs were performed. The eight ChSAT genes were divided into three branches, and the thirteen ChOASTL genes were divided into four branches by phylogenetic analysis and sequence alignment, indicating the evolutionary conservation of the gene structure and its association with other plant species. qRT-PCR analysis showed that the ChSAT and ChOASTL genes were differentially expressed in different tissues under various selenium levels, suggesting their important roles in Sec synthesis. The ChSAT1;2 and ChOASTLA1;2 were silenced by the VIGS system to investigate their involvement in selenium metabolites in C. hupingshanensis. The findings contribute to understanding the gene functions of ChSATs and ChOASTLs in the selenium stress and provide a reference for further exploration of the selenium metabolic pathway in plants.
Topics: Selenium; Molecular Docking Simulation; Gene Expression Regulation, Plant; Plant Proteins; Phylogeny; Cardamine; Metabolic Networks and Pathways; Acetyltransferases; Lyases
PubMed: 38775862
DOI: 10.1007/s00299-024-03227-6 -
Frontiers in Plant Science 2024Selenium (Se) deficiency, stemming from malnutrition in humans and animals, has the potential to disrupt many vital physiological processes, particularly those reliant...
INTRODUCTION
Selenium (Se) deficiency, stemming from malnutrition in humans and animals, has the potential to disrupt many vital physiological processes, particularly those reliant on specific selenoproteins. Agronomic biofortification of crops through the application of Se-containing sprays provides an efficient method to enhance the Se content in the harvested biomass. An optimal candidate for systematic enrichment, guaranteeing a broad trophic impact, must meet several criteria: (i) efficient accumulation of Se without compromising crop yield, (ii) effective conversion of mineral Se fertilizer into usable organically bound Se forms (Se), (iii) acceptance of a Se-enriched crop as livestock feed, and (iv), interest from the food processing industry in utilization of Se-enriched outputs. Hence, priority should be given to high-protein leafy crops, such as soybean.
METHODS
A three-year study in the Czech Republic was conducted to investigate the response of field-grown soybean plants to foliar application of NaSeO solutions (0, 15, 40, and 100 g/ha Se); measured outcomes included crop yield, Se distribution in aboveground biomass, and the chemical speciation of Se in seeds.
RESULTS AND DISCUSSION
Seed yield was unaffected by applied SeO , with Se content reaching levels as high as 16.2 mg/kg. The relationship between SeO dose and Se content in seeds followed a linear regression model. Notably, the soybeans demonstrated an impressive 73% average recovery of Se in seeds. Selenomethionine was identified as the predominant species of Se in enzymatic hydrolysates of soybean, constituting up to 95% of Se in seeds. Minor Se species, such as selenocystine, selenite, and selenate, were also detected. The timing of Se spraying influenced both plant SeO biotransformation and total content in seeds, emphasizing the critical importance of optimizing the biofortification protocol. Future research should explore the economic viability, long-term ecological sustainability, and the broad nutritional implications of incorporating Se-enriched soybeans into food for humans and animals.
PubMed: 38756968
DOI: 10.3389/fpls.2024.1379877 -
[Experimental study on promotion of peripheral nerve regeneration by selenium-methylselenocysteine].Zhongguo Xiu Fu Chong Jian Wai Ke Za... May 2024To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action.
OBJECTIVE
To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action.
METHODS
Rat Schwann cells RSC96 cells were randomly divided into 5 groups, which were group A (without any treatment, control group), group B (adding 100 μmol/L H O ), group C (adding 100 μmol/L H O +100 μmol/L SMC), group D (adding 100 μmol/L H O +200 μmol/L SMC), group E (adding 100 μmol/L H O +400 μmol/L SMC); the effect of SMC on cell proliferation was detected by MTT method, and the level of oxidative stress was detected by immunofluorescence for free radicals [reactive oxygen species (ROS)] after determining the appropriate dose group. Thirty-six 4-week-old male Sprague Dawley rats were randomly divided into 3 groups, namely, the sham operation group (Sham group), the sciatic nerve injury group (PNI group), and the SMC treatment group (SMC group), with 12 rats in each group; the rats in the PNI group were fed with food and water normally after modelling operation, and the rats in the SMC group were added 0.75 mg/kg SMC to the drinking water every day. At 4 weeks after operation, the sciatic nerves of rats in each group were sampled for neuroelectrophysiological detection of highest potential of compound muscle action potential (CMAP). The levels of inflammatory factors [interleukin 17 (IL-17), IL-6, IL-10 and oxidative stress factors catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)] were detected by ELISA assay. The luxol fast blue (LFB) staining was used to observe the myelin density, fluorescence intensity of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) was observed by immunofluorescence staining, and myelin morphology was observed by transmission electron microscopy with measurement of axon diameter. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2).
RESULTS
MTT assay showed that the addition of SMC significantly promoted the proliferation of RSC96 cells, and the low concentration could achieve an effective effect, so the treatment method of group C was selected for the subsequent experiments; ROS immunofluorescence test showed that group B showed a significant increase in the intensity of ROS fluorescence compared with that of group A, and group C showed a significant decrease in the intensity of ROS fluorescence compared with that of group B ( <0.05). Neuroelectrophysiological tests showed that the highest potential of CMAP in SMC group was significantly higher than that in PNI and Sham groups ( <0.05). ELISA assay showed that the levels of IL-6, IL-17, and MDA in PNI group were significantly higher than those in Sham group, and the levels of IL-10, SOD, and CAT were significantly lower; the levels of IL-6, IL-17, and MDA in SMC group were significantly lower than those in PNI group, and the levels of IL-10, SOD, and CAT were significantly higher ( <0.05). LFB staining and transmission electron microscopy showed that the myelin density and the diameter of axons in the SMC group were significantly higher than those of the PNI group and the Sham group ( <0.05). Immunofluorescence staining showed that the fluorescence intensity of GFAP and MBP in the SMC group were significantly stronger than those in the PNI group and Sham group ( <0.05). Western blot showed that the relative expressions of Nrf2 and HO-1 proteins in the SMC group were significantly higher than those in the PNI group and Sham group, and the ratio of p-p38MAPK/p38MAPK proteins was significantly higher in the PNI group than that in the SMC group and Sham group ( <0.05).
CONCLUSION
SMC may inhibit oxidative stress and inflammation after nerve injury by up-regulating the Nrf2/HO-1 pathway, and then inhibit the phosphorylation of p38MAPK pathway to promote the proliferation of Schwann cells, which ultimately promotes the formation of myelin sheaths and accelerates the regeneration of peripheral nerves.
Topics: Animals; Nerve Regeneration; Rats; Male; Selenocysteine; Rats, Sprague-Dawley; Schwann Cells; Oxidative Stress; Sciatic Nerve; Selenium; Cell Proliferation; Peripheral Nerve Injuries
PubMed: 38752248
DOI: 10.7507/1002-1892.202402031 -
Journal of the American Chemical Society Jun 2024Hydrogenases catalyze hydrogen/proton interconversion that is normally electrochemically reversible (having minimal overpotential requirement), a special property...
Replacing a Cysteine Ligand by Selenocysteine in a [NiFe]-Hydrogenase Unlocks Hydrogen Production Activity and Addresses the Role of Concerted Proton-Coupled Electron Transfer in Electrocatalytic Reversibility.
Hydrogenases catalyze hydrogen/proton interconversion that is normally electrochemically reversible (having minimal overpotential requirement), a special property otherwise almost exclusive to platinum metals. The mechanism of [NiFe]-hydrogenases includes a long-range proton-coupled electron-transfer process involving a specific Ni-coordinated cysteine and the carboxylate of a nearby glutamate. A variant in which this cysteine has been exchanged for selenocysteine displays two distinct changes in electrocatalytic properties, as determined by protein film voltammetry. First, proton reduction, even in the presence of H (a strong product inhibitor), is greatly enhanced relative to H oxidation: this result parallels a characteristic of natural [NiFeSe]-hydrogenases which are superior H production catalysts. Second, an inflection (an -shaped "twist" in the trace) appears around the formal potential, the small overpotentials introduced in each direction (oxidation and reduction) signaling a departure from electrocatalytic reversibility. Concerted proton-electron transfer offers a lower energy pathway compared to stepwise transfers. Given the much lower proton affinity of Se compared to that of S, the inflection provides compelling evidence that concerted proton-electron transfer is important in determining why [NiFe]-hydrogenases are reversible electrocatalysts.
Topics: Hydrogenase; Hydrogen; Protons; Electron Transport; Cysteine; Ligands; Selenocysteine; Catalysis; Electrochemical Techniques; Oxidation-Reduction
PubMed: 38747098
DOI: 10.1021/jacs.4c03489 -
Genome Research May 2024The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated...
The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, within both annotated protein-coding and noncoding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term ribosome decision graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the latter "translons." Nondeterministic events, such as initiation, reinitiation, selenocysteine insertion, or ribosomal frameshifting, are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions and for analyzing genetic variation and quantitative genome-wide data on translation for characterization of regulatory modulators of translation.
Topics: Ribosomes; Protein Biosynthesis; RNA, Messenger; Humans; Open Reading Frames; Eukaryota
PubMed: 38719470
DOI: 10.1101/gr.278810.123