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ChemMedChem May 2024The chemical and biological interest in this element and the molecules bearing selenium has been exponentially growing over the years. Selenium, formerly designated as a...
The chemical and biological interest in this element and the molecules bearing selenium has been exponentially growing over the years. Selenium, formerly designated as a toxin, becomes a vital trace element for life that appears as selenocysteine and its dimeric form, selenocystine, in the active sites of selenoproteins, which catalyze a wide variety of reactions, including the detoxification of reactive oxygen species and modulation of redox activities. From the point of view of drug developments, organoselenium drugs are isosteres of sulfur-containing and oxygen-containing drugs with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. This statement is the paramount relevance considering the big number of clinically employed compounds bearing sulfur or oxygen atoms if their structures including nucleosides and carbohydrates. Thus, in this article we have focused on the relevant features of the application of selenium in medicinal chemistry. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant published data on this subject, mainly concentrating the analysis on the last years. In consequence, the recent advances of relevant pharmacological organoselenium compounds are discussed.
PubMed: 38778500
DOI: 10.1002/cmdc.202400063 -
Biological Trace Element Research May 2024Selenium is an essential trace element co-translationally incorporated into selenoproteins with important biological functions. Health benefits have long been associated...
Selenium is an essential trace element co-translationally incorporated into selenoproteins with important biological functions. Health benefits have long been associated with selenium supplementation. However, cytotoxicity is observed upon excessive selenium intake. The aim of this study is to investigate the metabolic pathways underlying the response to the selenium-containing amino acids selenomethionine and selenocysteine in a normal human breast epithelial cell model. We show that both selenomethionine and selenocystine inhibit the proliferation of non-cancerous MCF-10A cells in the same concentration range as cancerous MCF-7 and Hela cells, which results in apoptotic cell death. Selenocystine exposure in MCF-10A cells caused a severe depletion of free low molecular weight thiols, which might explain the observed upregulation of the expression of the oxidative stress pathway transcription factor NRF2. Both selenomethionine and selenocystine induced the expression of target genes of the unfolded protein response (GRP78, ATF4, CHOP). Using a redox-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we show that both selenoamino acids shifted the ER redox balance towards an even more oxidizing environment. These results suggest that alteration of the redox state of the ER may disrupt protein folding and cause ER stress-induced apoptosis in MCF-10A cells exposed to selenoamino acids.
PubMed: 38777874
DOI: 10.1007/s12011-024-04244-y -
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 -
Biochimica Et Biophysica Acta.... Aug 2024Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading...
Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).
Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.
Topics: Female; Follicular Fluid; Insulin-Like Growth Factor I; Animals; Glutathione Peroxidase GPX1; Ovarian Cysts; Homeostasis; Selenocysteine; Oxidation-Reduction; Reactive Oxygen Species; Goats; Oxidative Stress; Glutathione Peroxidase; Oocytes; Humans; Ovarian Follicle; Proteomics
PubMed: 38744343
DOI: 10.1016/j.bbadis.2024.167235 -
Plant Physiology and Biochemistry : PPB Jun 2024Ostreococcus spp. are unicellular organisms with one of the simplest cellular organizations. The sequencing of the genomes of different Ostreococcus species has... (Review)
Review
Ostreococcus spp. are unicellular organisms with one of the simplest cellular organizations. The sequencing of the genomes of different Ostreococcus species has reinforced this status since Ostreococcus tauri has one most compact nuclear genomes among eukaryotic organisms. Despite this, it has retained a number of genes, setting it apart from other organisms with similar small genomes. Ostreococcus spp. feature a substantial number of selenocysteine-containing proteins, which, due to their higher catalytic activity compared to their selenium-lacking counterparts, may require a reduced quantity of proteins. Notably, O. tauri encodes several ammonium transporter genes, that may provide it with a competitive edge for acquiring nitrogen (N). This characteristic makes it an intriguing model for studying the efficient use of N in eukaryotes. Under conditions of low N availability, O. tauri utilizes N from abundant proteins or amino acids, such as L-arginine, similar to higher plants. However, the presence of a nitric oxide synthase (L-arg substrate) sheds light on a new metabolic pathway for L-arg in algae. The metabolic adaptations of O. tauri to day and night cycles offer valuable insights into carbon and iron metabolic configuration. O. tauri has evolved novel strategies to optimize iron uptake, lacking the classic components of the iron absorption mechanism. Overall, the cellular and genetic characteristics of Ostreococcus contribute to its evolutionary success, making it an excellent model for studying the physiological and genetic aspects of how green algae have adapted to the marine environment. Furthermore, given its potential for lipid accumulation and its marine habitat, it may represent a promising avenue for third-generation biofuels.
Topics: Adaptation, Physiological; Chlorophyceae; Chlorophyta; Nitrogen; Marine Biology
PubMed: 38735153
DOI: 10.1016/j.plaphy.2024.108661 -
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 -
Chemical Reviews May 2024Ribosome-dependent protein biosynthesis is an essential cellular process mediated by transfer RNAs (tRNAs). Generally, ribosomally synthesized proteins are limited to... (Review)
Review
Ribosome-dependent protein biosynthesis is an essential cellular process mediated by transfer RNAs (tRNAs). Generally, ribosomally synthesized proteins are limited to the 22 proteinogenic amino acids (pAAs: 20 l-α-amino acids present in the standard genetic code, selenocysteine, and pyrrolysine). However, engineering tRNAs for the ribosomal incorporation of non-proteinogenic monomers (npMs) as building blocks has led to the creation of unique polypeptides with broad applications in cellular biology, material science, spectroscopy, and pharmaceuticals. Ribosomal polymerization of these engineered polypeptides presents a variety of challenges for biochemists, as translation efficiency and fidelity is often insufficient when employing npMs. In this Review, we will focus on the methodologies for engineering tRNAs to overcome these issues and explore recent advances both and . These efforts include increasing orthogonality, recruiting essential translation factors, and creation of expanded genetic codes. After our review on the biochemical optimizations of tRNAs, we provide examples of their use in genetic code manipulation, with a focus on the discovery of bioactive macrocyclic peptides containing npMs. Finally, an analysis of the current state of tRNA engineering is presented, along with existing challenges and future perspectives for the field.
Topics: RNA, Transfer; Ribosomes; Protein Biosynthesis; Genetic Code; Humans
PubMed: 38688034
DOI: 10.1021/acs.chemrev.3c00894