Selenium-binding Protein Research Articles

SELENBP1 Inhibits the Warburg Effect and Tumor Growth by Reducing the HIF1α Expression in Colorectal Cancer.

Colorectal cancer (CRC) is experiencing a significant increase in both incidence and mortality rates globally. The expression of Selenium-binding protein 1 (SELENBP1) has been reported to be notably downregulated in various malignancies, yet its biological functions and cellular mechanisms in CRC remain incompletely understood. In our investigation, we observed the downregulation of SELENBP1 in CRC tissues through quantitative real-time PCR and western blotting and identified a positive correlation between higher SELENBP1 expression and improved survival prognosis using Kaplan-Meier survival analysis. Through loss-of-function and gain-of-function studies, we demonstrated the tumor-suppressive roles of SELENBP1 in CRC, supported by results from both in vitro and in vivo experiments. Furthermore, we uncovered the pivotal functions of SELENBP1 in suppressing aerobic glycolysis in CRC cells by regulating glucose uptake, lactate generation, and extracellular acidification rate. At a mechanistic level, we found that SELENBP1 inhibits the expression of the key glycolytic modulator hypoxia-inducible factor 1 subunit alpha (HIF1α), and the inhibition of glycolysis by SELENBP1 can be reversed by ectopic expression of HIF1α. Therefore, our study highlights the potential of SELENBP1 as a promising target for CRC therapy, given its significant impact on tumor suppression and reprogrammed glucose metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying CRC progression and may pave the way for the development of targeted therapies for this challenging disease.

Selenium-Binding Protein 1 (SBP1): A New Putative Player of Stress Sensing in Plants.

Selenium-binding proteins (SBPs) represent a ubiquitous and conserved protein family with yet unclear biochemical and molecular functions. The importance of the human homolog has been extensively studied as it is implicated in many cancer types and other diseases. On the other hand, little is known regarding plant homologs. In plants, there is evidence that SBP participates in developmental procedures, oxidative stress responses, selenium and cadmium binding, and pathogenic tolerance. Moreover, recent studies have revealed that SBP is a methanethiol oxidase (MTO) catalyzing the conversion of methanethiol into formaldehyde, H2S, and H2O2. The two later products emerge as key signal molecules, playing pivotal roles in physiological processes and environmental stress responses. In this review, we highlight the available information regarding plants in order to introduce and emphasize the importance of SBP1 and its role in plant growth, development, and abiotic/biotic stress.

PRDM1 promotes the ferroptosis and immune escape of thyroid cancer by regulating USP15-mediated SELENBP1 deubiquitination.

The deubiquitinating enzyme Ubiquitin-specific peptidase 15 (USP15) is upregulated in various cancers and promotes tumor progression by increasing the expression of several oncogenes. This project is designed to explore the role and mechanism of USP15 in thyroid cancer (TC) progression. Selenium-binding protein 1 (SELENBP1), USP15, CCL2/5, CXCL10/11, IL-4, and TGF-β1 mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). SELENBP1, USP15, GPX4, IL-10, Arg-1, Granzyme B, TNF-α, and PR domain zinc finger protein 1 (PRDM1) protein levels were examined by western blot assay. Fe+ level, malondialdehyde (MDA), and lipid-ROS levels were determined using special kits. The proportion of CD11b+CD206+ positive cells was detected using a flow cytometry assay. The role of SELENBP1 on TC cell growth was examined using a xenograft tumor model in vivo. After GeneMANIA prediction, the interaction between USP15 and SELENBP1 was verified using Co-immunoprecipitation (CoIP) assay. The binding between PRDM1 and USP15 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. SELENBP1 was increased in TC subjects and cell lines, and its knockdown repressed TC cell proliferation, migration, invasion, immune escape, and induced ferroptosis in vitro, as well as blocked tumor growth in vivo. In mechanism, USP15 interacted with SELENBP1 and maintained its stabilization by removing ubiquitin. Meanwhile, the upregulation of USP15 was induced by the transcription factor PRDM1. USP15 transcriptionally mediated by PRDM1 might boost TC cell malignant behaviors through deubiquitinating SELENBP1, providing a promising therapeutic target for TC treatment.

Overexpression of Wheat Selenium-Binding Protein Gene TaSBP-A Enhances Plant Growth and Grain Selenium Accumulation under Spraying Sodium Selenite.

Selenium (Se) is an essential trace element for humans. Low concentrations of Se can promote plant growth and development. Enhancing grain yield and crop Se content is significant, as major food crops generally have low Se content. Studies have shown that Se biofortification can significantly increase Se content in plant tissues. In this study, the genetic transformation of wheat was conducted to evaluate the agronomic traits of non-transgenic control and transgenic wheat before and after Se application. Se content, speciation, and transfer coefficients in wheat grains were detected. Molecular docking simulations and transcriptome data were utilized to explore the effects of selenium-binding protein-A TaSBP-A on wheat growth and grain Se accumulation and transport. The results showed that TaSBP-A gene overexpression significantly increased plant height (by 18.50%), number of spikelets (by 11.74%), and number of grains in a spike (by 35.66%) in wheat. Under normal growth conditions, Se content in transgenic wheat grains did not change significantly, but after applying sodium selenite, Se content in transgenic wheat grains significantly increased. Analysis of Se speciation revealed that organic forms of selenomethionine (SeMet) and selenocysteine (SeCys) predominated in both W48 and transgenic wheat grains. Moreover, TaSBP-A significantly increased the transfer coefficients of Se from solution to roots and from flag leaves to grains. Additionally, it was found that with the increase in TaSBP-A gene overexpression levels in transgenic wheat, the transfer coefficient of Se from flag leaves to grains also increased.

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.

Selenium binding protein 1 protects renal tubular epithelial cells from ferroptosis by upregulating glutathione peroxidase 4

Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression. In mouse renal ischemia-reperfusion injury (I/R), the rapid downregulation of SBP1 protein levels preceded downregulation of GPX4 and the onset of necrosis. In vitro, hypoxia/reoxygenation (H/R) stimulation in human proximal tubular epithelial (HK-2) cells induced ferroptotic cell death in associated with an acute reduction in SBP1 and GPX4 expression, and increased oxidative stress. Knockdown of SBP1 reduced GPX4 expression and increased the susceptibility of HK-2 cells to H/R-induced cell death, whereas overexpression of SBP1 reduced oxidative stress, maintained GPX4 expression, reduced mitochondrial damage, and reduced H/R-induced cell death. Finally, selenium deficiency reduced GPX4 expression and promoted H/R-induced cell death, whereas addition of selenium was protective against H/R-induced oxidative stress. In conclusion, SBP1 plays a functional role in hypoxia-induced tubular cell death. Enhancing SBP1 expression is a potential therapeutic approach for the treatment of AKI.

Gene expression and metabolite levels converge in the thermogenic spadix of skunk cabbage.

The inflorescence (spadix) of skunk cabbage (Symplocarpus renifolius) is strongly thermogenic and can regulate its temperature at around 23 °C even when the ambient temperature drops below freezing. To elucidate the mechanisms underlying developmentally controlled thermogenesis and thermoregulation in skunk cabbage, we conducted a comprehensive transcriptome and metabolome analysis across 3 developmental stages of spadix development. Our RNA-seq analysis revealed distinct groups of expressed genes, with selenium-binding protein 1/methanethiol oxidase (SBP1/MTO) exhibiting the highest levels in thermogenic florets. Notably, the expression of alternative oxidase (AOX) was consistently high from the prethermogenic stage through the thermogenic stage in the florets. Metabolome analysis showed that alterations in nucleotide levels correspond with the developmentally controlled and tissue-specific thermogenesis of skunk cabbage, evident by a substantial increase in AMP levels in thermogenic florets. Our study also reveals that hydrogen sulfide, a product of SBP1/MTO, inhibits cytochrome c oxidase (COX)-mediated mitochondrial respiration, while AOX-mediated respiration remains relatively unaffected. Specifically, at lower temperatures, the inhibitory effect of hydrogen sulfide on COX-mediated respiration increases, promoting a shift toward the dominance of AOX-mediated respiration. Finally, despite the differential regulation of genes and metabolites throughout spadix development, we observed a convergence of gene expression and metabolite accumulation patterns during thermogenesis. This synchrony may play a key role in developmentally regulated thermogenesis. Moreover, such convergence during the thermogenic stage in the spadix may provide a solid molecular basis for thermoregulation in skunk cabbage.

Dendropanoxide Attenuates High Glucose-induced Oxidative Damage in NRK-52E Cells via AKT/mTOR Signaling Pathway.

Hyperglycemia is a potent risk factor for the development and progression of diabetes-induced nephropathy. Dendropanoxide (DPx) is a natural compound isolated from Dendropanax morbifera (Araliaceae) that exerts various biological effects. However, the role of DPx in hyperglycemia-induced renal tubular cell injury remains unclear. The present study explored the protective mechanism of DPx on high glucose (HG)-induced cytotoxicity in kidney tubular epithelial NRK-52E cells. The cells were cultured with normal glucose (5.6 mM), HG (30 mM), HG + metformin (10 µM), or HG + DPx (10 µM) for 48 h, and cell cycle and apoptosis were analyzed. Malondialdehyde (MDA), advanced glycation end products (AGEs), and reactive oxygen species (ROS) were measured. Protein-based nephrotoxicity biomarkers were measured in both the culture media and cell lysates. MDA and AGEs were significantly increased in NRK-52E cells cultured with HG, and these levels were markedly reduced by pretreatment with DPx or metformin. DPx significantly reduced the levels of kidney injury molecule-1 (KIM-1), pyruvate kinase M2 (PKM2), selenium-binding protein 1 (SBP1), or neutrophil gelatinase-associated lipocalin (NGAL) in NRK-52E cells cultured under HG conditions. Furthermore, treatment with DPx significantly increased antioxidant enzyme activity. DPx protects against HG-induced renal tubular cell damage, which may be mediated by its ability to inhibit oxidative stress through the protein kinase B/mammalian target of the rapamycin (AKT/mTOR) signaling pathway. These findings suggest that DPx can be used as a new drug for the treatment of high glucose-induced diabetic nephropathy.

Serum Selenium-Binding Protein 1 (SELENBP1) in Burn Injury: A Potential Biomarker of Disease Severity and Clinical Course.

Oxidative stress, systemic inflammation, and metabolic derangements are hallmarks of burn pathophysiology. Severely burned patients are highly susceptible to infectious complications. Selenium-binding protein 1 (SELENBP1) modulates intracellular redox homeostasis, and elevated serum concentrations have been associated with adverse clinical outcomes in trauma patients. We hypothesized that serum SELENBP1 at hospital admission and during hospitalization may constitute a meaningful biomarker of disease severity and the clinical course in burn injury, with pulmonary infection as primary endpoint. To this end, we conducted a prospective cohort study that included 90 adult patients admitted to the Burn Center of the University Hospital Zurich, Switzerland. Patients were treated according to the local standard of care, with high-dose selenium supplementation during the first week. Serum SELENBP1 was determined at nine time-points up to six months postburn and the data were correlated to clinical parameters. SELENBP1 was initially elevated and rapidly declined within the first day. Baseline SELENBP1 levels correlated positively with the Abbreviated Burn Severity Index (ABSI) (R = 0.408; p < 0.0001). In multiple logistic regression, a higher ABSI was significantly associated with increased pulmonary infection risk (OR, 14.4; 95% CI, 3.2-88.8; p = 0.001). Similarly, baseline SELENBP1 levels constituted a novel but less accurate predictor of pulmonary infection risk (OR, 2.5; 95% CI, 0.7-8.9; p = 0.164). Further studies are needed to explore the additional value of serum SELENBP1 when stratifying patients with respect to the clinical course following major burns and, potentially, for monitoring therapeutic measures aimed at reducing tissue damage and oxidative stress.

Knocking out Selenium Binding Protein 1 Induces Depressive-Like Behavior in Mice.

Selenium binding protein 1 (SELENBP1) is involved in neurologic disorders, such as multiple sclerosis, spinal cord injury, Parkinson's disease, epilepsy, and schizophrenia. However, the role of SELENBP1 in the neurogenesis of depression, which is a neurologic disorder, and the underlying mechanisms of oxidative stress and inflammation in depression remain unknown. In this study, we evaluated the changes in the expression levels of SELENBP1 in the hippocampus of a mouse model of depression and in the serum of human patients with depression using the Gene Expression Omnibus database. These changes were validated using blood samples from human patients with depression and mouse models with chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. We also investigated the effects of SELENBP1 knockout (KO) on inflammation, oxidative stress, and hippocampal neurogenesis in mice with CUMS-induced depression. Our results revealed that SELENBP1 levels was decreased in the blood of human patients with depression and in the hippocampus of mice with CUMS-induced depression. SELENBP1 KO increased CUMS-induced depressive behavior in mice and caused dysregulation of inflammatory cytokines and oxidative stress. This led to a decrease in the numbers of doublecortin- and Ki67-positive cells, which might aggravate CUMS-induced depressive symptoms. These findings suggest that SELENBP1 might be involved in the regulation of neurogenesis in mice with depression and could be served as a potential target for diagnosing and treating depression.

Methanethiol: A Scent Mark of Dysregulated Sulfur Metabolism in Cancer.

In order to cope with increased demands for energy and metabolites as well as to enhance stress resilience, tumor cells develop various metabolic adaptations, representing a hallmark of cancer. In this regard, the dysregulation of sulfur metabolism that may result in elevated levels of volatile sulfur compounds (VSCs) in body fluids, breath, and/or excretions of cancer patients has recently gained attention. Besides hydrogen sulfide (H2S), methanethiol is the predominant cancer-associated VSC and has been proposed as a promising biomarker for non-invasive cancer diagnosis. Gut bacteria are the major exogenous source of exposure to this foul-smelling toxic gas, with methanethiol-producing strains such as Fusobacterium nucleatum highly abundant in the gut microbiome of colorectal carcinoma (CRC) patients. Physiologically, methanethiol becomes rapidly degraded through the methanethiol oxidase (MTO) activity of selenium-binding protein 1 (SELENBP1). However, SELENBP1, which is considered a tumor suppressor, is often downregulated in tumor tissues, and this has been epidemiologically linked to poor clinical outcomes. In addition to impaired removal, an increase in methanethiol levels may derive from non-enzymatic reactions, such as a Maillard reaction between glucose and methionine, two metabolites enriched in cancer cells. High methionine concentrations in cancer cells may also result in enzymatic methanethiol production in mitochondria. Moreover, enzymatic endogenous methanethiol production may occur through methyltransferase-like protein 7B (METTL7B), which is present at elevated levels in some cancers, including CRC and hepatocellular carcinoma (HCC). In conclusion, methanethiol contributes to the scent of cancer as part of the cancer-associated signature combination of volatile organic compounds (VOCs) that are increasingly being exploited for non-invasive early cancer diagnosis.

SBP1 promotes tumorigenesis of thyroid cancer through TXN/NIS pathway

BackgroundAs the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined.MethodsThe expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo.ResultsSBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors.ConclusionSBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.

Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions

BackgroundExtramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD.MethodsFrom 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared.ResultsThe NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047).ConclusionsWe defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.

Incorporation of Selenium Derived from Nanoparticles into Plant Proteins in Vivo.

Diets comprising selenium-deficient crops have been linked to immune disorders and cardiomyopathy. Selenium nanoparticles (SeNPs) have emerged as a promising nanoplatform for selenium-biofortified agriculture. However, SeNPs fail to reach field-scale applications due to a poor understanding of the fundamental principles of its behavior. Here, we describe the transport, transformation, and bioavailability of SeNPs through a combination of in vivo and in vitro experiments. We show synthesized amorphous SeNPs, when sprayed onto the leaves of Arabidopsis thaliana, are rapidly biotransformed into selenium(IV), nonspecifically incorporated as selenomethionine (SeMet), and specifically incorporated into two selenium-binding proteins (SBPs). The SBPs identified were linked to stress and reactive oxygen species (mainly H2O2 and O2-) reduction, processes that enhance plant growth and primary root elongation. Selenium is transported both upwards and downwards in the plant when SeNPs are sprayed onto the leaves. With the application of Silwet L-77 (a common agrochemical surfactant), selenium distributed throughout the whole plant including the roots, where pristine SeNPs cannot reach. Our results demonstrate that foliar application of SeNPs promotes plant growth without causing nanomaterial accumulation, offering an efficient way to obtain selenium-fortified agriculture.

Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small cell lung cancer.

Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium-containing protein as a mediator. Of note, the previous studies reported that the expression of selenium-binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non-small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. The expression of SELENBP1 was measured by qRT-PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK-8, colony formation, wound-haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT-II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase-3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.

Selenium-binding protein 1 (SELENBP1) is a copper-dependent thiol oxidase

Selenium-binding protein 1 (SELENBP1) was reported to act as a methanethiol oxidase (MTO) in humans, catalyzing the conversion of methanethiol to hydrogen peroxide, hydrogen sulfide and formaldehyde. Here, we identify copper ions as essential to this novel MTO activity. Site-directed mutagenesis of putative copper-binding sites in human SELENBP1 produced as recombinant protein in E. coli resulted in loss of its enzymatic function. On the other hand, the eponymous binding of selenium (as selenite) was no requirement for MTO activity and only moderately increased SELENBP1-catalyzed oxidation of methanethiol. Furthermore, SEMO-1, the SELENBP1 ortholog recently identified in the nematode C. elegans, also requires copper ions, and MTO activity was enhanced or abrogated, respectively, if worms were grown in the presence of cupric chloride or of a Cu chelator. In addition to methanethiol, we identified novel substrates of SELENBP1 from the group of volatile sulfur compounds, ranging from ethanethiol to 1-pentanethiol as well as 2-propene-1-thiol. Gut microbiome-derived methanethiol as well as food-derived volatile sulfur compounds (VSCs) account for malodors that may contribute to extraoral halitosis in humans, if not metabolized properly. As SELENBP1 is particularly abundant in tissues exposed to VSCs, such as colon, liver, and lung, it appears to contribute to copper-dependent VSC degradation.

Hydrogen sulfide (H2S) production by selenium-binding protein 1: SELENBP1 is a copper-dependent alkyl mercaptan oxidase (AMO)

Hydrogen sulfide (H2S) production by selenium-binding protein 1: SELENBP1 is a copper-dependent alkyl mercaptan oxidase (AMO)

Evolutionary Aspects of Selenium Binding Protein (SBP)

Selenium-binding proteins represent a ubiquitous protein family and recently SBP1 was described as a new stress response regulator in plants. SBP1 has been characterized as a methanethiol oxidase, however its exact role remains unclear. Moreover, in mammals, it is involved in the regulation of anti-carcinogenic growth and progression as well as reduction/oxidation modulation and detoxification. In this work, we delineate the functional potential of certain motifs of SBP in the context of evolutionary relationships. The phylogenetic profiling approach revealed the absence of SBP in the fungi phylum as well as in most non eukaryotic organisms. The phylogenetic tree also indicates the differentiation and evolution of characteristic SBP motifs. Main evolutionary events concern the CSSC motif for which Acidobacteria, Fungi and Archaea carry modifications. Moreover, the CC motif is harbored by some bacteria and remains conserved in Plants, while modified to CxxC in Animals. Thus, the characteristic sequence motifs of SBPs mainly appeared in Archaea and Bacteria and retained in Animals and Plants. Our results demonstrate the emergence of SBP from bacteria and most likely as a methanethiol oxidase.

Real-Time Monitoring of Selenium in Living Cells by Fluorescence Resonance Energy Transfer-Based Genetically Encoded Ratiometric Nanosensors.

Selenium is a component of selenoproteins, which plays a crucial role in cellular redox homeostasis, thyroid metabolism, and DNA synthesis. Selenium has pleiotropic effects like antioxidant and anti-inflammatory activities; however, excess intake of selenium can imbalance such processes. The effects of selenium on human health are numerous and complex, demanding additional research to monitor the flux rate of selenium. Here, we have created a noninvasive and highly efficient genetically encoded fluorescence resonance energy transfer (FRET)-based nanosensor, SelFS (Selenium FRET-Sensor), for real-time monitoring of selenium at the cellular and subcellular levels. The construct of the nanosensor contains a selenium-binding protein (SeBP) as the selenium-detecting element inserted between the green fluorescent protein variants enhanced cyan fluorescent protein and Venus. In the presence of selenium, SelFS brings a conformational change, which is seen in the form of FRET. In vitro studies showed that SelFS is highly specific and selective for selenium and stable at an altered pH range from 5.0 to 8.0. SelFS is a flexible and dynamic tool for the detection of selenium in both prokaryotes and eukaryotes in a noninvasive way, with a binding constant (K d) of 0.198 × 10-6 M as compared to its mutants. The developed nanosensor can provide us a reporter tool for a wide range of industrial and environmental applications, which will help us to understand its functions in biological systems.

The SAH7 Homologue of the Allergen Ole e 1 Interacts with the Putative Stress Sensor SBP1 (Selenium-Binding Protein 1) in Arabidopsis thaliana.

In this study, we focused on a member of the Ole e 1 domain-containing family, AtSAH7, in Arabidopsis thaliana. Our lab reports for the first time on this protein, AtSAH7, that was found to interact with Selenium-binding protein 1 (AtSBP1). We studied by GUS assisted promoter deletion analysis the expression pattern of AtSAH7 and determined that the sequence 1420 bp upstream of the transcription start can act as a minimal promoter inducing expression in vasculature tissues. Moreover, mRNA levels of AtSAH7 were acutely increased under selenite treatment in response to oxidative stress. We confirmed the aforementioned interaction in vivo, in silico and in planta. Following a bimolecular fluorescent complementation approach, we determined that the subcellular localization of the AtSAH7 and the AtSAH7/AtSBP1 interaction occur in the ER. Our results indicate the participation of AtSAH7 in a biochemical network regulated by selenite, possibly associated with responses to ROS production.