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Thioredoxin reductase

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https://www.readbyqxmd.com/read/28208651/the-architecture-of-thiol-antioxidant-systems-among-invertebrate-parasites
#1
Alberto Guevara-Flores, José de Jesús Martínez-González, Juan Luis Rendón, Irene Patricia Del Arenal
The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases...
February 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28193838/selenocysteine-insertion-at-a-predefined-uag-codon-in-a-release-factor-1-rf1-depleted-escherichia-coli-host-strain-bypasses-species-barriers-in-recombinant-selenoprotein-translation
#2
Qing Cheng, Elias S J Arnér
Selenoproteins contain the amino acid selenocysteine (Sec), co-translationally inserted at a predefined UGA opal codon by means of Sec-specific translation machineries. This process is in E. coli dependent upon binding of the Sec-dedicated elongation factor SelB to a SECIS element in the selenoprotein-encoding mRNA and competes with UGA-directed translational termination. Here we found that Sec can also be efficiently incorporated at a predefined UAG amber codon, thereby competing with RF1 rather than RF2. Subsequently utilizing the RF1 depleted E...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183062/thioredoxin-trxo1-interacts-with-proliferating-cell-nuclear-antigen-pcna-and-its-overexpression-affects-the-growth-of-tobacco-cell-culture
#3
Aingeru Calderón, Ana Ortiz-Espín, Raquel Iglesias-Fernández, Pilar Carbonero, Federico Vicente Pallardó, Francisca Sevilla, Ana Jiménez
Thioredoxins (Trxs), key components of cellular redox regulation, act by controlling the redox status of many target proteins, and have been shown to play an essential role in cell survival and growth. The presence of a Trx system in the nucleus has received little attention in plants, and the nuclear targets of plant Trxs have not been conclusively identified. Thus, very little is known about the function of Trxs in this cellular compartment. Previously, we studied the intracellular localization of PsTrxo1 and confirmed its presence in mitochondria and, interestingly, in the nucleus under standard growth conditions...
January 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28177228/design-synthesis-and-biological-evaluation-of-coupled-bioactive-scaffolds-as-potential-anticancer-agents-for-dual-targeting-of-dihydrofolate-reductase-and-thioredoxin-reductase
#4
Hui-Li Ng, Xiang Ma, Eng-Hui Chew, Wai-Keung Chui
The dihydrofolate reductase (DHFR) and thioredoxin reductase (TrxR) enzymes are involved in the process of tumor cell growth and survival. The 4,6-diamino-1,2-dihydro-1,3,5-triazine scaffold is well-established as a useful scaffold for DHFR inhibition, while chalcones have been reported to be inhibitors of TrxR. In this study, 15 novel compounds designed by the structural combination of the 4,6-diamino-1,2-dihydro-1,3,5-triazine and chalcone scaffolds via a di-ether linker were successfully synthesized and characterized...
February 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28158949/methionine-sulfoxide-reductase-a-deficiency-exacerbates-cisplatin-induced-nephrotoxicity-via-increased-mitochondrial-damage-and-renal-cell-death
#5
Mi Ra Noh, Ki Young Kim, Sang Jun Han, Jee In Kim, Hwa-Young Kim, Kwon Moo Park
AIMS: Methionine sulfoxide reductase A (MsrA), which is abundantly localized in the mitochondria, reduces methionine-S-sulfoxide scavenging reactive oxygen species (ROS). Cisplatin, an anticancer drug, accumulates at high levels in the mitochondria of renal cells, causing mitochondrial impairment that ultimately leads to nephrotoxicity. Here, we investigated the role of MsrA in cisplatin-induced mitochondrial damage and kidney cell death using MsrA gene-deleted (MsrA-/-) mice. RESULTS: Cisplatin injection resulted in increases of ROS production, methionine oxidation, and oxidative damage in the kidneys...
February 3, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28155927/mononuclear-gold-iii-complexes-with-l-histidine-containing-dipeptides-tuning-the-structural-and-biological-properties-by-variation-of-the-n-terminal-amino-acid-and-counter-anion
#6
Beata Warżajtis, Biljana Đ Glišić, Nada D Savić, Aleksandar Pavic, Sandra Vojnovic, Aleksandar Veselinović, Jasmina Nikodinovic-Runic, Urszula Rychlewska, Miloš I Djuran
Gold(iii) complexes with different l-histidine-containing dipeptides, [Au(Gly-l-His-NA,NP,N3)Cl]Cl·3H2O (1a), [Au(Gly-l-His-NA,NP,N3)Cl]NO3·1.25H2O (1b), [Au(l-Ala-l-His-NA,NP,N3)Cl][AuCl4]·H2O (2a), [Au(l-Ala-l-His-NA,NP,N3)Cl]NO3·2.5H2O (2b), [Au(l-Val-l-His-NA,NP,N3)Cl]Cl·2H2O (3), [Au(l-Leu-l-His-NA,NP,N3)Cl]Cl (4a) and [Au(l-Leu-l-His-NA,NP,N3)Cl][AuCl4]·H2O (4b), have been synthesized and structurally characterized by spectroscopic ((1)H NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques...
February 3, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28138683/designing-new-iridium-iii-arene-complexes-of-naphthoquinone-derivatives-as-anticancer-agents-a-structure-activity-relationship-study
#7
Leila Tabrizi, Hossein Chiniforoshan
A series of iridium(iii) arene complexes of naphthoquinone derivatives of the formula [Ir(III)(η(6)-L1)(L2)(3,5-(NO2)2pcyd)](PF6) (L1 = p-methylphenyl)ethynylferrocene; L2 = Lap: lapachol, 1, Plum: plumbagin, 2, Law: lawsone, 3, and Jug: juglone, 4; 3,5-(NO2)2pcyd = 3,5-dinitrophenylcyanamide) have been synthesized and investigated for their suitability as potential anticancer drugs. The DNA-binding interactions of the complexes with calf thymus DNA have been studied by absorption, emission, and viscosity measurements...
January 31, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28134858/docking-into-mycobacterium-tuberculosis-thioredoxin-reductase-protein-yields-pyrazolone-lead-molecules-for-methicillin-resistant-staphylococcus-aureus
#8
Noreena L Sweeney, Lauren Lipker, Alicia M Hanson, Chris J Bohl, Katie E Engel, Kelsey S Kalous, Mary E Stemper, Daniel S Sem, William R Schwan
The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S...
January 28, 2017: Antibiotics
https://www.readbyqxmd.com/read/28129719/differences-in-reperfusion-induced-mitochondrial-oxidative-stress-and-cell-death-between-hippocampal-ca1-and-ca3-subfields-is-due-to-the-mitochondrial-thioredoxin-system
#9
Bocheng Yin, German Barrionuevo, Ines Batinic-Haberle, Mats Sandberg, Stephen Weber
AIMS: The susceptibility of CA1 over CA3 to damage from cerebral ischemia may be related to the differences in reactive oxygen species (ROS) production/removal between the two hippocampal subfields. We aimed to measure CA1/CA3 differences in net ROS production in real time in the first thirty minutes of reperfusion in pyramidal cells. We aimed to determine the underlying cause of the differential vulnerability of CA1 and CA3. RESULTS: Real-time determinations of mitochondrial H2O2 and, independently, glutathione (GSH) redox status from roGFP-based probes in individual pyramidal cells in organotypic hippocampal cultures during oxygen-glucose deprivation (OGD)-reperfusion (RP) demonstrate a significantly more oxidizing environment during reperfusion in CA1 than CA3 mitochondria...
January 27, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28103771/structure-based-study-of-natural-products-with-anti-schistosoma-activity
#10
Ibezim Akachukwu, Olujide Oludayo Olubiyi, Ata Kosisochukwu, Mbah Chika John, Nwodo Ngozi Justina
: Background Schistosomiasis is a parasitic protozoal disease caused by flatworms of the genus Schistosoma. Although the disease threatens millions of lives, it is still at the top list of neglected tropical diseases and praziquantel, the only common schistosocidal drug in use, has records of decreasing efficiency and cases of resistance. Also, reports revealed that people in the rural areas, who are most affected, rely mostly on traditional herbal medicines because of limited access to modern healthcare...
January 19, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28101579/role-of-trna-selenocysteine-1-associated-protein-1-in-the-proliferation-and-apoptosis-of-cardiomyocyte%C3%A2-like-h9c2-cells
#11
Meng-Di Li, Wan-Peng Cheng, Min-Xia Shi, Tang-Dong Ge, Xiao-Lin Zheng, Dong-Yuan Wu, Xiao-Yan Hu, Jin-Cheng Luo, Feng-Lan Li, Hui Li
Transfer RNA selenocysteine 1 associated protein 1 (Trnau1ap) serves an essential role in the synthesis of selenoproteins, which have critical functions in numerous biological processes. Selenium deficiency results in a variety of diseases, including cardiac disease. However, the mechanisms underlying myocardial injury induced by selenium deficiency remain unclear. The present study examined the effects of Trnau1ap under‑ and overexpression in cardiomyocyte‑like H9c2 cells, by transfection with small interfering RNA and an overexpression plasmid, respectively...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098782/auranofin-inhibits-the-enzyme-activity-of-pasteurella-multocida-toxin-pmt-in-human-cells-and-protects-cells-from-intoxication
#12
Stefan Carle, Thorsten Brink, Joachim H C Orth, Klaus Aktories, Holger Barth
The AB-type protein toxin from Pasteurella multocida (PMT) contains a functionally important disulfide bond within its catalytic domain, which must be cleaved in the host cell cytosol to render the catalytic domain of PMT into its active conformation. Here, we found that the reductive potential of the cytosol of target cells, and more specifically, the activity of the thioredoxin reductase (TrxR) is crucial for this process. This was demonstrated by the strong inhibitory effect of the pharmacological TrxR inhibitor auranofin, which inhibited the intoxication of target cells with PMT, as determined by analyzing the PMT-catalyzed deamidation of GTP-binding proteins (G-proteins) in the cytosol of cells...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28093500/cytosolic-thioredoxin-reductase-1-is-required-for-correct-disulfide-formation-in-the-er
#13
Greg J Poet, Ojore Bv Oka, Marcel van Lith, Zhenbo Cao, Philip J Robinson, Marie Anne Pringle, Elias Sj Arnér, Neil J Bulleid
Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so-called non-native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non-native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non-native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1)...
January 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#14
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28052479/a-thioredoxin-nbtrxh2-from-nicotiana-benthamiana-negatively-regulates-the-movement-of-bamboo-mosaic-virus
#15
I-Hsuan Chen, Hui-Ting Chen, Ying-Ping Huang, Hweng-Jan Huang, Lin-Ling Shenkwen, Yau-Heiu Hsu, Ching-Hsiu Tsai
An upregulated gene derived from Bamboo mosaic virus (BaMV)-infected Nicotiana benthamiana plant was cloned and characterized in this study; BaMV is a single-stranded positive-sense RNA virus. This gene product, designated as NbTRXh2, was matched with sequences of thioredoxin h proteins, a group of small proteins with a conserved active-site motif WCXPC conferring disulfide reductase activity. To examine how NbTRXh2 is involved in the infection cycle of BaMV, we used the virus-induced gene silencing technique to knock down NbTRXh2 expression in N...
January 3, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28045936/detoxification-of-mitochondrial-oxidants-and-apoptotic-signaling-are-facilitated-by-thioredoxin-2-and-peroxiredoxin-3-during-hyperoxic-injury
#16
Benjamin J Forred, Darwin R Daugaard, Brianna K Titus, Ryan R Wood, Miranda J Floen, Michelle L Booze, Peter F Vitiello
Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2)...
2017: PloS One
https://www.readbyqxmd.com/read/28044432/from-structure-to-redox-the-diverse-functional-roles-of-disulfides-and-implications-in-disease
#17
REVIEW
Tyler J Bechtel, Eranthie Weerapana
This review provides a comprehensive overview of the functional roles of disulfide bonds and their relevance to human disease. The critical roles of disulfide bonds in protein structure stabilization and redox regulation of protein activity are addressed. Disulfide bonds are essential to the structural stability of many proteins within the secretory pathway and can exist as intramolecular or inter-domain disulfides. The proper formation of these bonds often relies on folding chaperones and oxidases such as members of the protein disulfide isomerase (PDI) family...
January 3, 2017: Proteomics
https://www.readbyqxmd.com/read/28028022/multiple-myeloma-cells-capacity-to-decompose-h2o2-determines-lenalidomide-sensitivity
#18
Sinto Sebastian, Yuan X Zhu, Esteban Braggio, Chang-Xin Shi, Sonali C Panchabhai, Scott A Van Wier, Greg J Ahmann, Marta Chesi, P Leif Bergsagel, A Keith Stewart, Rafael Fonseca
Lenalidomide is an immunomodulatory drug (IMiDs) with clinical efficacy in multiple myeloma (MM) and other late B-cell neoplasms. Although cereblon (CRBN) is an essential requirement for IMiD action, the complete molecular and biochemical mechanisms responsible for lenalidomide-mediated sensitivity or resistance remain unknown. Here, we report that IMiDs work primarily via inhibition of peroxidase-mediated intracellular H2O2 decomposition in MM cells. MM cells with lower H2O2-decomposition capacity were more vulnerable to lenalidomide-induced H2O2 accumulation and associated cytotoxicity...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28027877/hydrogen-sulfide-may-attenuate-methylmercury-induced-neurotoxicity-via-mitochondrial-preservation
#19
Junyan Han, Xuelian Yang, Xuehua Chen, Zhiqiang Li, Ming Fang, Bing Bai, Dehong Tan
Hydrogen sulfide (H2S) is a protective molecule and a novel gaseous mediator. Here we explored whether H2S donor (NaHS) could attenuate methylmercury (MeHg)-induced neurotoxicity in rats. The adult rats were randomly divided into four groups, i.e., control, NaHS, MeHg, and NaHS + MeHg groups. Rats of the NaHS + MeHg group were intraperitoneally (i.p) injected with 5.6 mg/kg/d of NaHS together with 5 μg/kg/d of MeHg. Rats of the MeHg group and NaHS group were injected with 5 μg/kg/d of MeHg and 5.6 mg/kg/d of NaHS, respectively...
February 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28017778/rhoa-s-nitrosylation-as-a-regulatory-mechanism-influencing-endothelial-barrier-function-in-response-to-g-bacterial-toxins
#20
F Chen, Y Wang, R Rafikov, S Haigh, W B Zhi, S Kumar, P T Doulias, O Rafikova, H Pillich, T Chakraborty, R Lucas, A D Verin, J D Catravas, J X She, S M Black, D J R Fulton
Disruption of the endothelial barrier in response to Gram positive (G(+)) bacterial toxins is a major complication of acute lung injury (ALI) and can be further aggravated by antibiotics which stimulate toxin release. The integrity of the pulmonary endothelial barrier is mediated by the balance of disruptive forces such as the small GTPase RhoA, and protective forces including endothelium-derived nitric oxide (NO). How NO protects against the barrier dysfunction is incompletely understood and our goal was to determine whether NO and S-nitrosylation can modulate RhoA activity and whether this mechanism is important for G(+) toxin-induced microvascular permeability...
December 22, 2016: Biochemical Pharmacology
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