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Thioredoxin reductase

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https://www.readbyqxmd.com/read/28640807/lack-of-a-peroxiredoxin-suppresses-the-lethality-of-cells-devoid-of-electron-donors-by-channelling-electrons-to-oxidized-ribonucleotide-reductase
#1
Susanna Boronat, Alba Domènech, Mercè Carmona, Sarela García-Santamarina, M Carmen Bañó, José Ayté, Elena Hidalgo
The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR). RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation...
June 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636040/tamoxifen-like-metallocifens-target-the-thioredoxin-system-determining-mitochondrial-impairment-leading-to-apoptosis-in-jurkat-cells
#2
Valeria Scalcon, Michèle Salmain, Alessandra Folda, Siden Top, Pascal Pigeon, Hui Zhi Shirley Lee, Gérard Jaouen, Alberto Bindoli, Anne Vessières, Maria Pia Rigobello
Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28629723/microbial-antioxidant-defense-enzymes
#3
REVIEW
Cindy Staerck, Amandine Gastebois, Patrick Vandeputte, Alphonse Calenda, Gérald Larcher, Louiza Gillmann, Nicolas Papon, Jean-Philippe Bouchara, Maxime J J Fleury
Free radicals are often described as chemical compounds characterized by unpaired electrons in their outer orbital rendering them highly reactive species. In mammalians, studies on free radicals were focused on reactive oxygen species (ROS) or reactive nitrogen species (RNS) due to their relative importance in physiological as well as in pathological processes. These cellular compounds are produced by different physiological systems such as the aerobic metabolism and play a major role in cell signaling pathways but also in the host immune defenses against pathogenic microorganisms...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28624622/preclinical-anti-cancer-activity-and-multiple-mechanisms-of-action-of-a-cationic-silver-complex-bearing-n-heterocyclic-carbene-ligands
#4
Simon J Allison, Maria Sadiq, Efstathia Baronou, Patricia A Cooper, Chris Dunnill, Nikolaos T Georgopoulos, Ayşe Latif, Samantha Shepherd, Steve D Shnyder, Ian J Stratford, Richard Wheelhouse, Charlotte Willans, Roger M Phillips
Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis...
June 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28620052/the-antibacterial-prodrug-activator-rv2466c-is-a-mycothiol-dependent-reductase-in-the-oxidative-stress-response-of-mycobacterium-tuberculosis
#5
Leonardo Astolfi Rosado, Khadija Wahni, Giulia Degiacomi, Brandan Pedre, David Young, Alfonso G de la Rubia, Francesca Boldrin, Edo Martens, Laura Marcos-Pascual, Enea Sancho-Vaello, David Albesa-Jové, Roberta Provvedi, Charlotte Martin, Vadim Makarov, Wim Versées, Guido Verniest, Marcelo E Guerin, Luis M Mateos, Riccardo Manganelli, Joris Messens
The Mycobacterium tuberculosis rv2466c gene encodes an oxidoreductase enzyme annotated as DsbA. It has a CPWC active-site motif embedded within its thioredoxin-fold domain and mediates the activation of the prodrug TP053, a thienopyrimidine derivative that kills both replicating and nonreplicating bacilli. However, its mode of action and actual enzymatic function in M. tuberculosis have remained enigmatic. In this study, we report that Rv2466c is essential for bacterial survival under H2O2 stress. Further, we discovered that Rv2466c lacks oxidase activity; rather, it receives electrons through the mycothiol/mycothione reductase/NADPH pathway to activate TP053, preferentially via a dithiol-disulfide mechanism...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28606995/synergistic-antibacterial-effect-of-silver-and-ebselen-against-multidrug-resistant-gram-negative-bacterial-infections
#6
Lili Zou, Jun Lu, Jun Wang, Xiaoyuan Ren, Lanlan Zhang, Yu Gao, Martin E Rottenberg, Arne Holmgren
Multidrug-resistant (MDR) Gram-negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult-to-treat MDR Gram-negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28603024/functional-research-and-molecular-mechanism-of-kainic-acid-induced-denitrosylation-of-thioredoxin-1-in-rat-hippocampus
#7
Hongning Yang, Ningjun Zhao, Lanxin Lv, Xianliang Yan, Shuqun Hu, Tie Xu
Thioredoxin-1 (Trx1) has long been recognized as a redox regulator, and is implicated in the inhibition of cell apoptosis. Trx1 is essential for the maintenance of the S-nitrosylation of molecules in cells. The S-nitrosylation of Trx1 is essential for the physiological function such as preservation of the redox regulatory activity. The mechanisms underlying Trx1 denitrosylation induced by kainate acid (KA) injection still remain uncharacterized. Our results showed that the S-nitrosylation levels of Trx1 were decreased subsequent to KA injection and that the glutamate receptor 6 (GluR6) antagonist NS102 could inhibit the denitrosylation of Trx1...
June 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28600984/impaired-cross-talk-between-the-thioredoxin-and-glutathione-systems-is-related-to-ask-1-mediated-apoptosis-in-neuronal-cells-exposed-to-mercury
#8
Vasco Branco, Lucia Coppo, Susana Solá, Jun Lu, Cecília M P Rodrigues, Arne Holmgren, Cristina Carvalho
Mercury (Hg) compounds target both cysteine (Cys) and selenocysteine (Sec) residues in peptides and proteins. Thus, the components of the two major cellular antioxidant systems - glutathione (GSH) and thioredoxin (Trx) systems - are likely targets for mercurials. Hg exposure results in GSH depletion and Trx and thioredoxin reductase (TrxR) are prime targets for mercury. These systems have a wide-range of common functions and interaction between their components has been reported. However, toxic effects over both systems are normally treated as isolated events...
June 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28571752/insights-into-the-differential-toxicological-and-antioxidant-effects-of-4-phenylchalcogenil-7-chloroquinolines-in-caenorhabditis-elegans
#9
Willian G Salgueiro, Bruna S Goldani, Tanara V Peres, Antonio Miranda-Vizuete, Michael Aschner, João Batista Teixeira da Rocha, Diego Alves, Daiana S Ávila
Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C...
May 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28560500/synergistic-induction-of-apoptosis-by-combination-treatment-with-mesupron-and-auranofin-in-human-breast-cancer-cells
#10
Joo-Eun Lee, Yeo-Jung Kwon, Hyoung-Seok Baek, Dong-Jin Ye, Eunah Cho, Hyung-Kyoon Choi, Kyung-Soo Oh, Young-Jin Chun
Urokinase-type plasminogen activator (uPA) has been validated as a predictive or prognostic biomarker protein, and mesupron is considered the first-in-class anticancer agent to inhibit uPA activity in human breast cancer. In the present study, we showed that the synergism between mesupron and auranofin, a thioredoxin reductase inhibitor, for inducing of apoptosis in MCF-7 human breast cancer cells. Our results demonstrated that mesupron and auranofin significantly lead to inhibition of the cancer cells proliferation; cell cycle arrest at the G1/S phase of the cell cycle, and apoptosis as indicated by caspase 3 activation, poly(ADP-ribose) polymerase cleavage, and annexin V staining...
May 31, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28551108/brevetoxin-2-is-a-unique-inhibitor-of-the-c-terminal-redox-center-of-mammalian-thioredoxin-reductase-1
#11
Wei Chen, Anupama Tuladhar, Shantelle Rolle, Yanhao Lai, Freddy Rodriguez Del Rey, Cristian E Zavala, Yuan Liu, Kathleen S Rein
Karenia brevis, the Florida red tide dinoflagellate produces a suite of neurotoxins known as the brevetoxins. The most abundant of the brevetoxins PbTx-2, was found to inhibit the thioredoxin-thioredoxin reductase system, whereas the PbTx-3 has no effect on this system. On the other hand, PbTx-2 activates the reduction of small disulfides such as 5,5'-dithio-bis-(2-nitrobenzoic acid) by thioredoxin reductase. PbTx-2 has an α, β-unsaturated aldehyde moiety which functions as an efficient electrophile and selenocysteine conjugates are readily formed...
May 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28544404/microrna-328-is-involved-in-the-effect-of-selenium-on-hydrogen-peroxide-induced-injury-in-h9c2-cells
#12
Xiaolin Zheng, Xiaoyan Hu, Tangdong Ge, Mengdi Li, Minxia Shi, Jincheng Luo, Hehuan Lai, Tingting Nie, Fenglan Li, Hui Li
Oxidative stress induces apoptosis in cardiac cells, and antioxidants attenuate the injury. MicroRNAs (miRNAs) are also involved in cell death; therefore, this study aimed to investigate the role of miRNAs in the effect of selenium on oxidative stress-induced apoptosis. The effects of sodium selenite were analyzed via cell viability, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration. Flow cytometry was used to evaluate cell apoptosis. Fura-2AM was used to calculate intracellular Ca(2+) concentration...
May 25, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28542579/transcriptomic-dissection-reveals-wide-spread-differential-expression-in-chickpea-during-early-time-points-of-fusarium-oxysporum-f-sp-ciceri-race-1-attack
#13
Sumanti Gupta, Anirban Bhar, Moniya Chatterjee, Amartya Ghosh, Sampa Das
Plants' reaction to underground microorganisms is complex as sessile nature of plants compels them to prioritize their responses to diverse microorganisms both pathogenic and symbiotic. Roots of important crops are directly exposed to diverse microorganisms, but investigations involving root pathogens are significantly less. Thus, more studies involving root pathogens and their target crops are necessitated to enrich the understanding of underground interactions. Present study reported the molecular complexities in chickpea during Fusarium oxysporum f...
2017: PloS One
https://www.readbyqxmd.com/read/28536696/txnrd1-is-an-unfavorable-prognostic-factor-for-patients-with-hepatocellular-carcinoma
#14
Binsheng Fu, Wei Meng, Xiancheng Zeng, Hui Zhao, Wei Liu, Tong Zhang
Thioredoxin reductase 1 (TXNRD1) which is a selenocysteine-containing protein is overexpressed in many malignancies. Its role in the hepatocellular carcinoma (HCC) prognosis has not been investigated. In this study, we investigated whether TXNRD1 functions as an independent prognostic factor for HCC patients. We found TXNRD1 was overexpressed in HCC tissues and cells, immunohistochemical analysis suggested TXNRD1 was elevated in 57 of 120 (47.5%) clinical samples, and its level was increased with the increasing clinical stage...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28512695/arsenic-induces-thioredoxin-1-and-apoptosis-in-human-liver-hhl-5-cells
#15
Yuanyuan Li, Yuanyuan Zhang, Yanhui Gao, Wei Zhang, Xiaohui Cui, Junqiu Liu, Yudan Wei
To further characterize the mechanisms underlying liver toxicity induced by arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and the apoptotic signaling pathways in human liver HHL-5 cells. The cells were treated with 0, 2, 5, and 10 μM of sodium arsenite for 24 h, and the changes of Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis were examined. A concentration-dependent increase in mRNA and protein levels of Trx1 and TrxR1 was observed in arsenic-treated cells...
May 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28506882/examination-of-the-superoxide-hydrogen-peroxide-forming-and-quenching-potential-of-mouse-liver-mitochondria
#16
Liam Slade, Julia Chalker, Nidhi Kuksal, Adrian Young, Danielle Gardiner, Ryan J Mailloux
Pyruvate dehydrogenase (PDHC) and α-ketoglutarate dehydrogenase complex (KGDHC) are important sources of reactive oxygen species (ROS). In addition, it has been found that mitochondria can also serve as sinks for cellular hydrogen peroxide (H2O2). However, the ROS forming and quenching capacity of liver mitochondria has never been thoroughly examined. Here, we show that mouse liver mitochondria use catalase, glutathione (GSH), and peroxiredoxin (PRX) systems to quench ROS. Incubation of mitochondria with catalase inhibitor 3-amino-1,2,4-triazole (triazole) induced a significant increase in pyruvate or α-ketoglutarate driven O2(-)/H2O2 formation...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28500266/n-terminal-thioredoxin-reductase-domains-and-thioredoxins-act-concertedly-in-seedling-development
#17
Valle Ojeda, Juan M Pérez-Ruiz, María-Cruz González, Victoria A Nájera, Mariam Sahrawy, Antonio Jesús Serrato, Peter Geigenberger, Francisco J Cejudo
Thiol-dependent redox regulation of enzyme activity plays a central role in the rapid acclimation of chloroplast metabolism to ever fluctuating light availability. This regulatory mechanism relies on ferredoxin (Fdx) reduced by the photosynthetic electron transport chain, which fuels reducing power to thioredoxins (Trxs) via a Fdx-dependent Trx reductase (FTR). In addition, chloroplasts harbour an NADPH-dependent Trx reductase, which has a joint Trx domain at the C-terminus, termed NTRC. Thus, a relevant issue in chloroplast function is to establish the relationship between these two redox systems and its impact on plant development...
May 12, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28495429/superoxide-hydrogen-peroxide-genetic-imbalance-modulates-differentially-the-oxidative-metabolism-on-human-peripheral-blood-mononuclear-cells-exposed-to-seleno-l-methionine
#18
Karen Lilian Schott, Charles Elias Assmann, Fernanda Barbisan, Verônica Farina Azzolin, Beatriz Bonadiman, Marta Maria Medeiros Frescura Duarte, Alencar Kolinski Machado, Ivana Beatrice Mânica da Cruz
Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several diseases. Into mitochondria, MnSOD catalyses superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest HP concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are essential to HP removal produced in excess in cells...
May 8, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28487966/oligomeric-proanthocyanidins-protects-a549-cells-against-h2o2-induced-oxidative-stress-via-the-nrf2-are-pathway
#19
Chao Sun, Weiguo Jin, Hongcan Shi
Oxidative signaling and oxidative stress contribute to aging, cancer and diseases resulting from lung fibrosis. In this study, we explored the anti-oxidative potential of oligomeric proanthocyanidins (OPCs), natural flavonoid compounds. We examined the protective effects of OPCs against hydrogen peroxide (H2O2)-induced oxidative stress in non-small cell lung cancer cells (A549). We demonstrated that OPC markedly attenuated H2O2-induced A549 cell viability, as shown by by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) assay...
June 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28487964/effects-of-the-cyclophilin-type-peptidylprolyl-cis-trans-isomerase-from-pyropia-yezoensis-against-hydrogen-peroxide-induced-oxidative-stress-in-hepg2-cells
#20
Eun-Young Kim, Youn Hee Choi, Chang Geun Choi, Taek-Jeong Nam
The present study aimed to describe the expression and purification of cyclophilin-type peptidylprolyl cis-trans isomerase (PPI) from the red alga Pyropia yezoensis. The antioxidant activity of the purified protein was also demonstrated, based on its ability to act against oxidative stress in HepG2 human hepatocellular carcinoma cells. HepG2 cells that were treated with recombinant PPI protein exhibited a reduction in the formation of hydrogen peroxide (H2O2)‑mediated reactive oxygen species (ROS). In HepG2 cells, treatment of recombinant PPI protein expression diminished H2O2‑mediated oxidative stress and restored both the expression and the activity of certain antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and thioredoxin reductase (TRR)...
June 2017: Molecular Medicine Reports
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