Speciation of Selenium Nanoparticles and Other Selenium Species in Soil: Simple Extraction Followed by Membrane Separation and ICP-MS Determination.

The application of selenium nanoparticle (SeNP)-based fertilizers can cause SeNPs to enter the soil environment. Considering the possible transformation of SeNPs and the species-dependent toxicity of selenium (Se), accurate analysis of SeNPs and other Se species present in the soil would help rationally assess the potential hazards of SeNPs to soil organisms. Herein, a novel method for speciation of SeNPs and other Se species in soil was established. Under the optimized conditions, SeNPs, selenite, selenate, and seleno amino acid could be simultaneously extracted from the soil with mixtures of tetrasodium pyrophosphate (5 mM) and potassium dihydrogen phosphate (1.2 µM), while inert Se species (mainly metal selenide) remained in the soil. Then, extracted SeNPs can be effectively captured by a nylon membrane (0.45 µm) and quantified by inductively coupled plasma mass spectrometry (ICP-MS). Other extracted Se species can be separated and quantified by high-performance liquid chromatography coupled with ICP-MS. Based on the difference between the total Se contents and extracted Se contents, the amount of metal selenide can be calculated. The limits of detection of the method were 0.02 µg/g for SeNPs, 0.05 µg/g for selenite, selenate, and selenocystine, and 0.25 µg/g for selenomethionine, respectively. Spiking experiments also showed that our method was applicable to real soil sample analysis. The present method contributes to understanding the speciation of Se in the soil environment and further estimating the occurrence and application risks of SeNPs.

Click Chemistry of Selenium Dihalides: Novel Bicyclic Organoselenium Compounds Based on Selenenylation/Bis-Functionalization Reactions and Evaluation of Glutathione Peroxidase-like Activity.

A number of highly efficient methods for the preparation of novel derivatives of 9-selenabicyclo[3.3.1]nonane in high yields based on selenium dibromide and cis,cis-1,5-cyclooctadiene are reported. The one-pot syntheses of 2,6-diorganyloxy-9-selenabicyclo[3.3.1]nonanes using various O-nucleophiles including alkanols, phenols, benzyl, allyl, and propargyl alcohols were developed. New 2,6-bis(1,2,3-triazol-1-yl)-9-selenabicyclo[3.3.1]nonanes were obtained by the copper-catalyzed 1,3-dipolar cycloaddition of 2,6-diazido-9-selenabicyclo[3.3.1]nonane with unsubstituted gaseous acetylene and propargyl alcohol. The synthesis of 2,6-bis(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonane, based on the generation of corresponding dithiolate anion from bis[amino(iminio)methylsulfanyl]-9-selenabicyclo[3.3.1]nonane dibromide, followed by the nucleophilic addition of the dithiolate anion to unsubstituted acetylene, was developed. The glutathione peroxidase-like activity of the obtained water-soluble products was estimated and compounds with high activity were found. Overall, 2,6-Diazido-9-selenabicyclo[3.3.1]nonane exhibits the highest activity among the obtained compounds.

The compound-independent calibration of five selenium species in rice using ion-pairing reversed phase chromatography coupled to inductively coupled plasma tandem mass spectrometry.

An enzyme-assisted extraction and an ion pairing reversed phase chromatography (IP-RPC) coupled to inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) method were established for the simultaneous analysis of five selenium species in rice: selenious acid (SeIV), selenic acid (SeVI), selenocystine (SeCys2), methylselenocysteine (SeMeCys) and selenomethionine (SeMet). Optimal extraction efficiencies were obtained by using 15 mg protease XIV, water bath temperature of 45°C, pH of 6.5 and incubation of six hours. The total extracted Se species account for 92.5-109.3 % of the total Se in rice. The instrumental limits of detection for five selenium species ranged from 0.04 to 0.12 ng Se g-1. Spike recovery experiments performed on rice samples were in the range of 96.1-102.9 % for all analytes except for SeCys2 (66.1-77.1 %). A consistency of Se elemental response was observed among Se species analyzed in this study as the ratio of linear equation slope ranged from 1.020 to 1.036 (SeIV as reference) in rice matrix. The developed compound-independent calibration method was applied to detect Se species in eleven rice samples from China. Both selenium-enriched rice and regular rice were predominated with SeMet, accounting for ∼89.4 % of total selenium.

Identification of γ-Glutamyl-Selenomethionine as the Principal Selenium Metabolite in a Selenium-Enriched Probiotic, Bifidobacterium longum, by Two-Dimensional HPLC-ICP MS and HPLC-ESI Orbitrap MS.

Selenium (Se)-enriched probiotics are potential sources of organic Se in the human diet, but their application in food is debated because most selenized probiotics and their metabolites are not well-characterized. We analyzed a Se-enriched probiotic, Bifidobacterium longum DD98, to unveil its Se metabolite profiles by two-dimensional high-performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP MS) and HPLC-electrospray ionization Orbitrap MS. A major Se metabolite was identified as gamma-glutamyl-selenomethionine (γ-Glu-SeMet), which accounted for 42.5 ± 3.4% of water-soluble Se. Most of the remaining Se was present as SeMet (35.2 ± 0.6%) in a free or protein-bound form. In addition, 11 minor Se metabolites were identified, eight of which had not been reported before in probiotics. Six of the identified compounds contained γ-Glu-SeMet as the core structure, constituting a γ-Glu-SeMet family. This study demonstrates the presence of γ-Glu-SeMet in a probiotic, showing a different selenite metabolite pathway from that of Se-enriched yeast, and it offers an alternative and potentially attractive source of organic Se for food and feed supplementation.

Assay of selenol species in biological samples by the fluorescent probe Sel-green.

Selenium (Se) is an essential trace element for diverse cellular functions. The biological significance of Se is predominantly dependent on its incorporation into the selenocysteine (Sec) for synthesis of selenoproteins (SePs), such as thioredoxin reductase family enzymes and glutathione peroxidase family enzymes. In general, the hyperactivity of the selenol group in Sec confers the Sec residue critical for functions of SePs. The Sec is much less abundant than its sulfur analog cysteine (Cys), and it remains a high challenge to detect Sec, especially in complex biological samples. We recently reported a selective fluorescent probe Sel-green for selenols and summarized the principles for design of selenol (and thiophenol) probes. Sel-green discriminates selenols from other biological species, especially thiols, under physiological conditions, and has been applied to detect both endogenous and exogenous selenol species in live cells. In this chapter, we describe a protocol and guideline for the selective detection of Sec by applying the Sel-green. This protocol is also suitable for detection of other selenol species. This practical and convenient assay would assist scientists to better understand the pivotal roles of Sec as well as SePs.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo.

The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1ß, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.

Synthesis and Evaluation of Antioxidant, Anti-Edematogenic and Antinociceptive Properties of Selenium-Sulfa Compounds.

Herein we describe results for the synthesis and synthetic application of 4-amino-3-(arylselenyl)benzenesulfonamides, and preliminary evaluation of antioxidant, anti-edematogenic and antinociceptive properties. This class of compounds was synthesized in good yields by a reaction of commercially available sulfanilamide and diorganyl diselenides in the presence of 10 mol% of I2 . Furthermore, the synthesized compound 4-amino-3-(phenylselenyl)benzenesulfonamide (3 a) was evaluated on complete Freund's adjuvant (CFA)-induced acute inflammatory pain. Dose- and time-response curves of antinociceptive effect of compound 3 a were performed using this experimental model. Also, the effect of compound 3 a was monitored in a hot-plate test to evaluate the acute non-inflammatory antinociception. The open-field test was performed to evaluate the locomotor and exploratory behaviors of mice. Oxidative stress markers, such as glutathione peroxidase activity; reactive species, non-protein thiols, and lipid peroxidation levels were performed to investigate the antioxidant action of compound 3 a. Our findings suggest that the antioxidant effect of compound 3 a may contribute to reducing the nociception and suppress the signaling pathways of inflammation on the local injury induced by CFA. Thus, compound 3 a reduced the paw edema as well as the hyperalgesic behavior in mice, being a promising therapeutic agent for the treatment of painful conditions.

The Pharmacology and Therapeutic Utility of Sodium Hydroselenide.

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe-/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.

Emerging role of selenium in treatment of rheumatoid arthritis: An insight on its antioxidant properties.

Rheumatoid Arthritis is an inflammatory disease primarily involves the inflamed synovium, affecting about 0.5-1 % population worldwide. It is the assumption from many years that oxidative stress is involved in the pathophysiology of inflammatory disorders like RA and many others. The significance of micronutrients in arthritis is linked to their role as a cofactor for the activation of selenoenzymes. Dietary interventions can manage the clinical symptoms of RA like pain, swelling and tenderness of joints and their associated disability along the progression of disease. This review highlights the antioxidant potential of selenium in treatment of RA along with the scientific evidence that Se supplementation can reduce disease progression by managing its clinical symptoms.

Neuroprotective Effect of 3-[(4-Chlorophenyl)selanyl]-1-methyl-1H-indole on Hydrogen Peroxide-Induced Oxidative Stress in SH-SY5Y Cells.

Extensive data have reported the involvement of oxidative stress in the pathogenesis of neuropsychiatric disorders, prompting the pursuit of antioxidant molecules that could become adjuvant pharmacological agents for the management of oxidative stress-associated disorders. The 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has been reported as an antioxidant and immunomodulatory compound that improves depression-like behavior and cognitive impairment in mice. However, the exact effect of CMI on specific brain cells is yet to be studied. In this context, the present study aimed to evaluate the antioxidant activity of CMI in H2O2-induced oxidative stress on human dopaminergic neuroblastoma cells (SH-SY5Y) and to shed some light into its possible mechanism of action. Our results demonstrated that the treatment of SH-SY5Y cells with 4 µM CMI protected them against H2O2 (343 µM)-induced oxidative stress. Specifically, CMI prevented the increased number of reactive oxygen species (ROS)-positive cells induced by H2O2 exposure. Furthermore, CMI treatment increased the levels of reduced glutathione in SH-SY5Y cells. Molecular docking studies demonstrated that CMI might interact with enzymes involved in glutathione metabolism (i.e., glutathione peroxidase and glutathione reductase) and H2O2 scavenging (i.e., catalase). In silico pharmacokinetics analysis predicted that CMI might be well absorbed, metabolized, and excreted, and able to cross the blood-brain barrier. Also, CMI was not considered toxic overall. Taken together, our results suggest that CMI protects dopaminergic neurons from H2O2-induced stress by lowering ROS levels and boosting the glutathione system. These results will facilitate the clinical application of CMI to treat nervous system diseases associated with oxidative stress.

Optimization of elemental selenium (Se(0)) determination in yeasts by anion-exchange HPLC-ICP-MS.

An analytical method was developed for the speciation of elemental selenium (Se(0)) in selenized yeasts by anion-exchange HPLC-ICP-MS after its chemical transformation into SeSO32- by reaction with sodium sulfite. The presence of Se(0) in the yeasts was further confirmed by single-particle ICP-MS. Indeed, Se nanoparticles, if present, are expected to be, at least partly, Se(0). X-ray photoelectron spectroscopy, a well-recognized technique for chemical element speciation in the solid state, was also used with this objective. Both methods were able to confirm the presence of Se(0) in the selenized yeasts but failed to provide reliable quantitative results. Analytical performances of the HPLC-ICP-MS method were then evaluated for Se(0) determination. Quantification limits of 1 mg/kg were reached. The recovery levels from an added quantity comprised between 93 and 101%. Within-run and between-run precisions were both below 8%. The procedure developed was finally applied to quantify Se(0) content in a series of seven yeast batches from different suppliers. Se(0) was found to be present in all the studied yeasts and represented on average 10-15% of the total Se.

SiOxNy back-contact barriers for CZTSe thin-film solar cells.

The formation of molybdenum diselenide (MoSe2) is widely observed at the back-contact interface for copper zinc tin selenide (CZTSe) thin-film solar cells. Depending on individual selenium (Se) supply and thermal conditions for forming CZTSe absorbers on molybdenum (Mo) substrates, the thickness of MoSe2 can vary from a few hundreds of nanometers up to ≈ 1 µm, which is comparable to the commonly adopted thickness of 1 ~ 1.5 µm for CZTSe absorbers. In this study, for controlling the thickness of interfacial MoSe2, thin diffusion barrier layers of silicon oxynitride (SiOxNy) are deposited onto Mo layers prior to the growth of CZTSe absorbers in the fabrication process. As a result, a reduction in the thicknesses of MoSe2 layers is achieved. In terms of energy conversion efficiency (η), CZTSe solar cells grown on Mo/SiOxNy back contacts suffer a deterioration as the SiOxNy layers get thicker. CZTSe solar cells grown on Mo/SiOxNy/Mo back contacts preserve their efficiencies at ≈ 11% with thin 10 nm SiOxNy layers.

New Selenonapthaquinone-Based Copper (II) Complexes as the Next-Generation Photochemotherapeutic Agents.

BACKGROUND AND OBJECTIVE: Photoactive transition metal complexes like copper complexes find great interest in promoting metal-based photochemotherapeutic agents. In the present study, we explored the photocytotoxic efficacy of new selenylnaphthoquinone-based copper (II) complexes that provide a phenomenal platform in making an effective photo-chemotherapeutic agent via PDT in the clinical field of cancer therapy. METHODS: Three new copper(II) complexes (1-3) were synthesized in 40-60% yield and characterized analytically/ spectroscopically. ATCC® Normal Adult Human Primary Epidermal Keratinocytes were grown in Dermal Cell Basal Media supplemented with Keratinocyte Growth Kit components, to propagate keratinocytes in serum- free (not animal free) conditions. Anticancer activity of the complexes was studied using MTT (3- [4,5- dimethyltiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay. The intracellular ROS (1O2) generation was studied by using Flow Cytometric Analysis (FACS) on HaCaT cells using cell accessible non-polar 2',7'- Dichlorofluorescein Diacetate (DCFH-DA) dye. The Acridine Orange/Ethidium Bromide (AO/EB) dual staining assay was performed for detecting apoptosis in HaCaT cells. Several photophysical studies probing the generation of singlet oxygen was also carried out. We have performed Time-Dependent Density Functional Theory (TD-DFT) calculations using unrestricted B3LYP to understand the mechanism of type-II process. RESULTS: All the complexes were remarkably cytotoxic in HaCaT cells with IC50, 1-4µM under visible light with comparing lower dark toxicity. The presence of low-lying and long-lived triplet excited state allowed effective intersystem crossing and subsequent generation of singlet oxygen, which was the primary cytotoxic species responsible for oxidative stress and apoptosis. The experimental findings are in good agrrement with the computational analysis (TD-DFT). CONCLUSION: The remarkably enhanced cytotoxicity of the new selenyl copper (II) complexes under the visible light probed the role of Se in photosensitized generation of singlet oxygen which was responsible for apoptosis in HaCaT cells. The results in the present work are of paramount importance in developing next generation copper(II)-based PDT agents.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50 °C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe = 866.0 ppm), 125Te{1H} (δTe = 422.0 ppm) and 31P{1H} (δP = -1.0, -13.0 and -15.0 ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened in vitro and ex vivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

Regulation of Selenium/Sulfur Interactions to Enhance Chemopreventive Effects: Lessons to Learn from Brassicaceae.

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations' health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications' experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs.

Influence of Fluorine Substituents on the Electronic Properties of Selenium-N-Heterocyclic Carbene Compounds.

N-heterocyclic carbenes (NHCs) are common ancillary ligands in organometallic compounds that are used to alter the electronic and steric properties of a metal centre. To date, various NHCs have been synthesised with different electronic properties, which can be done by modifying the backbone or changing the nitrogen substituents group. This study describes a systematic modification of NHCs by the inclusion of fluorine substituents and examines the use of selenium-NHC compounds to measure the π-accepting ability of these fluorinated NHC ligands. Evaluation of the 77Se NMR chemical shifts of the selenium adducts reveals that fluorinated NHCs have higher chemical shifts than the non-fluorinated counterparts, IMes and IPh. Higher 77Se NMR chemical shifts values indicate a stronger π-accepting ability of the NHC ligands. The findings of this study suggest that the presence of fluorine atoms has increased the π-accepting ability of the corresponding NHC ligands. This work supports the advantage of the 77Se NMR chemical shifts of selenium-NHC compounds for assessing the influence of fluorine substituents on NHC ligands.

Virtual screening and assessment of anticancer potential of selenium-based compounds against HL-60 and MCF7 cells.

Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3, 6, 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.

High-Performance Core/Shell of ZnO/TiO2 Nanowire with AgCl-Doped CdSe Quantum Dots Arrays as Electron Transport Layer for Perovskite Solar Cells.

Most previous studies of perovskite core/shell structures have been based on ZnO/TiO2 nanowires (NWs), which are not suitable for high photoelectric conversion efficiency. Here, core/shell ZnO/TiO2 NWs with AgCl-doped CdSe quantum dots were fabricated as an electron transport layer (ETL) for perovskite solar cells, based on ZnO/TiO2 arrays. We designed CdSe with AgCl dopants that were synthesized by a colloidal process. An improvement of the recombination barrier (Rct1), due to shell supplementation with AgCl-doped CdSe quantum dots, improved the open circuit voltage, the fill factor, and the adsorption capacity of CH3NH3PbI3 perovskite with NWs. The enhanced cell steady state was attributable to TiO2 with AgCl-doped CdSe QD supplementation. A maximum power conversion efficiency of 15.12% was attained in an atmospheric environment. The mechanism of the recombination and electron transport in the perovskite solar cells becoming the basis of ZnO/TiO2 core/shell arrays was investigated to represent the merit of ZnO/TiO2 core/shell arrays as an electron transport layer in effective devices. These results showed an uncomplicated approach for restraining non-radiative recombination loss in hetero-structure core/shell arrays to significantly improve perovskite solar cell performance and increase the effectiveness of photovoltaics.

Production of a Urinary Selenium Metabolite, Trimethylselenonium, by Thiopurine S-Methyltransferase and Indolethylamine N-Methyltransferase.

Selenium (Se) is an essential trace element in animals; however, the element can become highly toxic in excess amounts beyond the nutritional level. Although Se is mainly excreted into urine as a selenosugar within the nutritional level, excess amounts of Se are transformed as an alternative urinary metabolite, trimethylselenonium ion (TMSe). Se methylation appears to be an important metabolic process for the detoxification of excess Se; however, the biochemical mechanisms underlying the Se methylation have not been elucidated. In this study, we evaluated biochemical characteristics of two human methyltransferases for Se methylation, thiopurine S-methyltransferase (TPMT) and indolethylamine N-methyltransferase (INMT). The first methylation of Se, i.e., a nonmethylated to a monomethylated form, was specifically driven by TPMT, and INMT specifically mediated the third methylation, i.e., dimethylated to trimethylated form. The second methylation, i.e., a monomethylated to dimethylated form, was driven by either TPMT or INMT. Exogenous expression of TPMT, but not INMT, ameliorated the cytotoxicity of inorganic nonmethylated selenium salt, suggesting that only TPMT gave the cellular resistance against selenite exposure. TPMT was ubiquitously expressed in most mouse tissues and preferably expressed in the liver and kidneys, while INMT was specifically expressed in the lung and supplementally expressed in the liver and kidneys. Our results revealed that both TPMT and INMT cooperatively contributed to the TMSe production, enabling urinary excretion of Se and maintenance of homeostasis of this essential yet highly toxic trace element. Thus, TPMT and INMT can be recognized as selenium methyltransferases as a synonym.