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Thioredoxin reductase

N Connor Payne, Drew R Barber, Erik L Ruggles, Robert J Hondal
Dimedone is a widely used reagent to assess the redox state of cysteine-containing proteins as it will alkylate sulfenic acid residues, but not sulfinic acid residues. While it has been reported that dimedone can label selenenic acid residues in selenoproteins, we investigated the stability, and reversibility of this label in a model peptide system. We also wondered whether dimedone could be used to detect seleninic acid residues. We used benzenesulfinic acid, benzeneseleninic acid, and model selenocysteine-containing peptides to investigate possible reactions with dimedone...
February 16, 2018: Protein Science: a Publication of the Protein Society
Piergiorgio Stevanato, Chiara Broccanello, Vita M C Moliterni, Giuseppe Mandolino, Valeria Barone, Luigi Lucini, Giovanni Bertoldo, Marco Bertaggia, Massimo Cagnin, Diego Pizzeghello, Andrea Baglieri, Andrea Squartini, Giuseppe Concheri, Serenella Nardi
In this study, a system based on omics profiling was set-up for sugar beet ( Beta vulgaris L. subsp. vulgaris ) evaluation after changes in sulfate availability. Seedlings were grown on sulfate-deprived Hoagland solution. Six days after germination, 100 μM MgSO 4 was added to the solution. Root samples were collected 36 h after treatments. WinRHIZO root-scanning approach was used for the automated image analysis of plant root morphology. Inductively Coupled Plasma Spectrometry (ICP-OES) and quadrupole-time-of-flight mass spectrometry (Q-TOF) were used for ionomic and metabolic analysis, respectively...
2018: Frontiers in Plant Science
William C Stafford, Xiaoxiao Peng, Maria Hägg Olofsson, Xiaonan Zhang, Diane K Luci, Li Lu, Qing Cheng, Lionel Trésaugues, Thomas S Dexheimer, Nathan P Coussens, Martin Augsten, Hanna-Stina Martinsson Ahlzén, Owe Orwar, Arne Östman, Sharon Stone-Elander, David J Maloney, Ajit Jadhav, Anton Simeonov, Stig Linder, Elias S J Arnér
Cancer cells adapt to their inherently increased oxidative stress through activation of the glutathione (GSH) and thioredoxin (TXN) systems. Inhibition of both of these systems effectively kills cancer cells, but such broad inhibition of antioxidant activity also kills normal cells, which is highly unwanted in a clinical setting. We therefore evaluated targeting of the TXN pathway alone and, more specifically, selective inhibition of the cytosolic selenocysteine-containing enzyme TXN reductase 1 (TXNRD1). TXNRD1 inhibitors were discovered in a large screening effort and displayed increased specificity compared to pan-TXNRD inhibitors, such as auranofin, that also inhibit the mitochondrial enzyme TXNRD2 and additional targets...
February 14, 2018: Science Translational Medicine
Tao Su, Meiru Si, Yunfeng Zhao, Yan Liu, Shumin Yao, Chengchuan Che, Can Chen
Peroxiredoxin Q (PrxQ) that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions...
2018: PloS One
Andrea Silvestrini, Alvaro Mordente, Giuseppe Martino, Carmine Bruno, Edoardo Vergani, Elisabetta Meucci, Antonio Mancini
Selenium is a trace element, nutritionally classified as essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is here extensively described. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases...
January 31, 2018: Current Medicinal Chemistry
Zhenbo Cao, Lorna Mitchell, Oliver Hsia, Miriam Scarpa, Stuart T Caldwell, Arina D Alfred, Alexandra Gennaris, Jean-Francois Collet, Richard C Hartley, Neil J Bulleid
The oxidation of methionine residues in proteins occurs during oxidative stress and can lead to an alteration in protein function.  The enzyme methionine sulfoxide reductase reverses this modification.  Here we characterise the mammalian enzyme methionine sulfoxide reductase B3.  There are two splice variants of this enzyme that differ only in their N-terminal signal sequence, which directs the protein to either the ER or mitochondria.  We demonstrate here that the enzyme can complement a bacterial strain which is dependent upon methionine sulfoxide reduction for growth, that the purified recombinant protein is enzymatically active showing stereospecificity towards R -methionine sulfoxide, and identify the active site and two resolving cysteine residues...
February 2, 2018: Biochemical Journal
Zhi-Xian Yin, Wei Hang, Gang Liu, Yi-Shu Wang, Xiang-Feng Shen, Qian-Hui Sun, Dong-Dong Li, Yong-Ping Jian, Yang-He Zhang, Cheng-Shi Quan, Qinghua Zeng, Yu-Lin Li, Rui-Xun Zhao, Qiang Ding, Zhi-Xiang Xu
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Mutations of TP53 may reach 70% - 85% in HNSCC patients without human papillomavirus (HPV) infection. Recurrence rate remains particularly high for HNSCC patients with mutations in the TP53 gene although patients are responsive to surgery, irradiation, and chemotherapy early in the treatment. p53-Reactivation and Induction of Massive Apoptosis-1 (PRIMA-1) and its methylated analogue PRIMA-1 Met (also known as APR-246) are quinuclidine compounds that rescue the DNA-binding activity of mutant p53 (mut-p53) and restore the potential of wild-type p53...
January 5, 2018: Oncotarget
Paweł Paśko, Krzysztof Okoń, Mirosław Krośniak, Ewelina Prochownik, Paweł Żmudzki, Jadwiga Kryczyk-Kozioł, Paweł Zagrodzki
Rutabaga sprouts belong to the Brassicaceae family and may exert a negative influence on thyroid function, because they are a rich in glucosinolates. These sprouts are also valuable source of iodine (6.5 ± 0.6 μg/100 g of fresh weight). Sprouts were tested in a long-term experiment with young male rats as an element of their diet, combined with two models of hypothyroidism, the first - deficit of iodine and the second - sulfadimethoxine ingestion as a pharmacological agent caused inhibition of thyroid peroxidase...
March 2018: Journal of Trace Elements in Medicine and Biology
Yanfang Ouyang, Yi Peng, Jing Li, Arne Holmgren, Jun Lu
The thioredoxin and glutaredoxin systems possess a variety of biological activities in mammalian cells, including the defense against oxidative stress, regulation of DNA synthesis, the cell cycle and the mediation of apoptosis. The thioredoxin system, comprised of NADPH, thioredoxin reductase (TrxR) and thioredoxin (Trx), exerts its activities via a disulfide-dithiol exchange reaction. Mammalian TrxRs are selenoproteins; the thiols and selenols in the active site of these enzymes confer the thioredoxin system to work as soft bases, which have a high affinity with soft acids, including numerous metal ions...
February 7, 2018: Metallomics: Integrated Biometal Science
D B Shpakovsky, A A Shtil, E V Kharitonashvili, V Yu Tyurin, T A Antonenko, A A Nazarov, V P Osipova, N T Berberova, L S Foteeva, C Schmidt, I Ott, E R Milaeva
Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry. Among gold pharmaceuticals, auranofin is a well known antirheumatic drug. The efficacy of gold-organic complexes largely depends on their pro-oxidant properties since auranofin targets the redox enzyme thioredoxin reductase (TrxR). However, an uncontrollable oxygen burst may be harmful for healthy cells; therefore, the search for chemical modifications to attenuate oxidation-related general toxicity of gold containing anti-inflammatory drugs is justified...
February 5, 2018: Metallomics: Integrated Biometal Science
Moritz Oberstadt, Jens Stieler, David Larbi Simpong, Ute Römuß, Nicole Urban, Michael Schaefer, Thomas Arendt, Max Holzer
Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disease, which is characterized by a rapid loss of lower and upper motor neurons. As a major neuropathological hallmark, protein aggregates containing the Transactivating Response Region (TAR) DNA Binding Protein (TDP-43) are detectable in about 95% of sporadic ALS patients. TDP-43 interacts with itself physiologically to form liquid droplets, which may progress to pathological aggregates. In this study, we established the NanoBit luciferase complementation assay to measure TDP-43 self-interaction and found the fusion of the split luciferase subunits to the N-terminus of the protein as the strongest interacting partners...
February 2, 2018: Scientific Reports
Hui Li, Qiang He, Fanzhi Meng, Xu Feng, Jiang Chen, Libo Li, Jinghua Liu
Methionine sulfoxide reductase B1 (MsrB1), a member of the selenoprotein family and contributes significantly to the reduction of methionine sulfoxides produced from reactive oxygen species (ROS). However, few studies have examined the role of MsrB1 in tumors. Here We tested the proliferation and invasion in MsrB1 knockdown u2os cells under H2O2/thioredoxin. As shown in our result, knockdown of MsrB1 inhibited the proliferation of u2os cells and regulates mitogen-activated protein kinase (MAPK) pathway by down-regulation of Erk, MeK phosphorylation and p53 expression in u2os cells...
January 29, 2018: Biochemical and Biophysical Research Communications
F Tonolo, M Sandre, S Ferro, A Folda, V Scalcon, G Scutari, E Feller, O Marin, A Bindoli, M P Rigobello
Milk and milk-derived products are a relevant source of bioactive peptides, which are also potential components of functional foods. Bioactive peptides exert multiple actions including an antioxidant role. In the present paper, four synthetic peptides (NPYVPR, AVPYPQR, KVLPVPEK, and ARHPHPHLSFM), corresponding to milk-derived peptides were studied. Although with different features, as revealed by RP-HPLC chromatography and MS analysis, the obtained peptides were shown to be taken up by Caco-2 cells arranged in an epithelial monolayer formation...
February 1, 2018: Food & Function
Gong Chen, Qiong Chen, Fanxu Zeng, Liang Zeng, Haiyan Yang, Yi Xiong, Chunhua Zhou, Li Liu, Wenjuan Jiang, Nong Yang, Yongchang Zhang
Background: The thioredxin reductases 1 (TrxR1) is one of the major antioxidant and redox regulators in mammalian cells. Studies have shown that TrxR1 is over expressed in many malignancy diseases. However, few studies have evaluated the role of TrxR1 in non-small cell lung cancer (NSCLC). Methods: Serum levels of TrxR1 and CEA in 142 patients with EGFR wild type and ALK negative advanced NSCLC was measured by ELISA assay before first line standard doublet chemotherapy from June 2013 to February 2016 in Hunan Cancer Hospital...
December 29, 2017: Oncotarget
Moran Benhar
Mammalian cells employ elaborate antioxidant systems to effectively handle reactive oxygen and nitrogen species (ROS and RNS). At the heart of these systems operate two selenoprotein families consisting of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) enzymes. Although mostly studied in the context of oxidative stress, considerable evidence has amassed to indicate that these selenoenzymes also play important roles in nitrosative stress responses. GPx and TrxR, together with their redox partners, metabolize nitrosothiols and peroxynitrite, two major RNS...
January 25, 2018: Free Radical Biology & Medicine
Roxanne P Smith, Andrew E Whitten, Jason J Paxman, Charlene M Kahler, Martin J Scanlon, Begoña Heras
The membrane protein DsbD is a reductase that acts as an electron hub, translocating reducing equivalents from cytoplasmic thioredoxin to a number of periplasmic substrates involved in oxidative protein folding, cytochrome c maturation and oxidative stress defence. DsbD is a multi-domain protein consisting of a transmembrane domain (t-DsbD) flanked by two periplasmic domains (n-DsbD and c-DsbD). Previous studies have shown that DsbD is required for the survival of the obligate human pathogen Neisseria meningitidis...
January 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Alessio Metere, Francesca Frezzotti, Claire Elizabeth Graves, Massimo Vergine, Alessandro De Luca, Donatella Pietraforte, Laura Giacomelli
Background: Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells...
2018: Cancer Cell International
Qian Li, Rui Li, Stephanie B Wall, Katelyn Dunigan, Changchun Ren, Tamas Jilling, Lynette K Rogers, Trent E Tipple
We previously showed that the thioredoxin reductase-1 (TrxR1) inhibitor aurothioglucose (ATG) improves alveolarization in hyperoxia-exposed newborn C3H/HeN mice. Our data supported a mechanism by which the protective effects of ATG are mediated via sustained nuclear factor E2-related factor 2 (Nrf2) activation in hyperoxia-exposed C3H/HeN mice 72 h after ATG administration. Given that inbred mouse strains have differential sensitivity and endogenous Nrf2 activation by hyperoxia, the present studies utilized two C57Bl/6 exposure models to evaluate the effects of ATG on lung development and Nrf2 activation...
January 25, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Mari L Sbardelotto, Giulia S Pedroso, Fernanda T Pereira, Helen R Soratto, Stella Ms Brescianini, Pauline S Effting, Anand Thirupathi, Renata T Nesi, Paulo Cl Silveira, Ricardo A Pinho
Regular exercise can decrease the deleterious effects of aging and limit the development and progression of chronic disease in elderly people, depending on the type, intensity, frequency, and duration of exercise. This study aimed to investigate the potential protective effects of different physical training programs on oxidative stress parameters and inflammatory and neurotrophic mediators in the serum of elderly men. Healthy male volunteers [60 to 80 years; n=55] were divided into four groups: control [Ctr, n=14], aerobic training on dry land [ATdl, n=12]; and combined training on dry land [CTdl, n=12] or in water [CTw, n=17]...
December 2017: Aging and Disease
Devin A Hudson, Jeffrey L Caplan, Colin Thorpe
The development of genetically encoded fluorescent probes for analyte-specific imaging has revolutionized our understanding of intracellular processes. Current classes of intracellular probes depend on the selection of binding domains that either undergo conformational changes on analyte binding or can be linked to thiol redox chemistry. Here we have designed novel probes by fusing a flavoenzyme, whose fluorescence is quenched on reduction by the analyte of interest, with a GFP domain to allow for rapid and specific ratiometric sensing...
January 17, 2018: Biochemistry
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