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Thioredoxin reductase

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https://www.readbyqxmd.com/read/28098782/auranofin-inhibits-the-enzyme-activity-of-pasteurella-multocida-toxin-pmt-in-human-cells-and-protects-cells-from-intoxication
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
December 24, 2016: 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
#9
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 V 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
https://www.readbyqxmd.com/read/28011872/functional-significance-of-nadph-thioredoxin-reductase-c-in-the-antioxidant-defense-system-of-cyanobacterium-anabaena-sp-pcc-7120
#10
Shoko Mihara, Keisuke Yoshida, Akiyoshi Higo, Toru Hisabori
The redox regulation system is widely accepted as a crucial mechanism for controlling the activities of various metabolic enzymes. In addition to thioredoxin reductase/thioredoxin cascades, NADPH-thioredoxin reductase C (NTRC), a hybrid protein formed by an NADPH-thioredoxin reductase domain and a thioredoxin (Trx) domain, is present in chloroplasts and in most cyanobacteria species. Although several target proteins and physiological functions of NTRC in chloroplasts have been characterized, little is known about NTRC functions in cyanobacteria...
December 22, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28009916/selenium-in-the-prevention-of-atherosclerosis-and-its-underlying-mechanisms
#11
REVIEW
Hongmei Liu, Huibi Xu, Kaixun Huang
Atherosclerosis and related cardiovascular diseases (CVDs) represent the greatest threats to human health worldwide. Selenium, an essential trace element, is incorporated into selenoproteins that play a crucial role in human health and disease. Although findings from a limited number of randomized trials have been inconsistent and cannot support a protective role of Se supplementation in CVDs, prospective observational studies have generally shown a significant inverse association between selenium or selenoprotein status and CVD risk...
December 23, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28008954/sodium-selenate-regulates-the-brain-ionome-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#12
Lin Zheng, Hua-Zhang Zhu, Bing-Tao Wang, Qiong-Hui Zhao, Xiu-Bo Du, Yi Zheng, Liang Jiang, Jia-Zuan Ni, Yan Zhang, Qiong Liu
Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer's disease (AD) progression. It was recently reported that selenium could reverse memory deficits in AD mouse model. We carried out multi-time-point ionome analysis to investigate the interactions among 15 elements in the brain by using a triple-transgenic mouse model of AD with/without high-dose sodium selenate supplementation. Except selenium, the majority of significantly changed elements showed a reduced level after 6-month selenate supplementation, especially iron whose levels were completely reversed to normal state at almost all examined time points...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28001402/anticancer-and-antiangiogenic-iron-ii-complexes-that-target-thioredoxin-reductase-to-trigger-cancer-cell-apoptosis
#13
Lina Xie, Zuandi Luo, Zhennan Zhao, Tianfeng Chen
Thioredoxin reductase (TrxR) is a selenoenzyme that could regulate intracellular oxidative balance and found to be overexpressed in many human tumor cells. Due to its important role in cancer progression, TrxR is becoming an attractive target in chemotherapeutic drug design. In this study, a new class of Fe(II) complexes with phenanthroline derivatives as ligands were synthesized and characterized. The mechanism of cell death induced by complex 3 revealed that the growth of cancer cells was suppressed by apoptosis and specifically inhibited the activities of TrxR...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27993729/modulation-of-signaling-mechanisms-in-the-heart-by-thioredoxin-1
#14
REVIEW
Narayani Nagarajan, Shinichi Oka, Junichi Sadoshima
Myocardial ischemia/reperfusion and heart failure are the major cardiac conditions in which an imbalance between oxidative stress and anti-oxidant mechanisms is observed. The myocardium has endogenous reducing mechanisms, including the thioredoxin (Trx) and glutathione systems, that act to scavenge reactive oxygen species (ROS) and reduce oxidized proteins. The Trx system consists of Trx, Trx reductase (TrxR), and an electron donor, NADPH, where Trx is maintained in a reduced state in the presence of TrxR and NADPH...
December 16, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27977313/thioredoxin-reductase-inhibitors-a-patent-review
#15
Baoxin Zhang, Junmin Zhang, Shoujiao Peng, Ruijuan Liu, Xinming Li, Yanan Hou, Xiao Han, Jianguo Fang
Mammalian thioredoxin reductases (TrxRs) are selenocysteine-containing homodimeric flavin enzymes that catalyze the NADPH-dependent reduction of oxidized thioredoxins. Increasing evidence indicates that TrxRs are potential targets for anticancer drug development. This review summarizes patented inhibitors of mammalian TrxRs with an emphasis on those having potential applications in treatment of cancer. Areas covered: A background introduction of TrxR as well as the relevance of TrxR and cancer is provided in the first part of this review...
December 26, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27938548/-effect-of-oxidative-stress-associated-damage-to-the-lung-tissue-caused-by-different-body-mass-index-in-the-rat-models
#16
X Y Li, X J Zhang, J H Zhao, J Y Xu
Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months...
December 12, 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27933898/versiquinazolines-a-k-fumiquinazoline-type-alkaloids-from-the-gorgonian-derived-fungus-aspergillus-versicolor-lzd-14-1
#17
Zhongbin Cheng, Lanlan Lou, Dong Liu, Xiaodan Li, Peter Proksch, Sheng Yin, Wenhan Lin
Eleven fumiquinazoline-type alkaloids, namely, versiquinazolines A-K (1-11), along with cottoquinazolines B-D, were isolated from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1. Their structures were determined by extensive analyses of the spectroscopic data (1D and 2D NMR, HRESIMS), in addition to the experimental and calculated ECD data and X-ray single-crystal diffraction analysis for the assignments of the absolute configurations. Versiquinazolines A, B, and F (1, 2, and 6), bearing a methanediamine or an aminomethanol unit and representing a unique subtype of fumiquinazolines, were found from nature for the first time...
November 23, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27920018/a-phase-ii-randomized-placebo-controlled-trial-of-oral-n-acetylcysteine-for-protection-of-melanocytic-nevi-against-uv-induced-oxidative-stress-in-vivo
#18
Pamela B Cassidy, Tong Liu, Scott R Florell, Matthew Honeggar, Sancy A Leachman, Kenneth M Boucher, Douglas Grossman
Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator...
January 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27917873/dose-biomarker-response-modeling-of-the-anticancer-effect-of-ethaselen-in-a-human-non-small-cell-lung-cancer-xenograft-mouse-model
#19
Suo-Fu Ye, Jian Li, Shuang-Min Ji, Hui-Hui Zeng, Wei Lu
Thioredoxin reductase (TrxR) is a component of several redox-sensitive signaling cascades that mediate important biological processes such as cell survival, maturation, growth, migration and inhibition of apoptosis. The expression levels of TrxR1 in some human carcinoma cell lines are nearly 10 times higher than those in normal cells. Ethaselen is a novel antitumor candidate that exerts potent inhibition on non-small cell lung cancer (NSCLC) by targeting TrxR. In this study we explored the relationship between the ethaselen dose and TrxR activity level and the relationship between TrxR degradation and tumor apoptosis in a human lung carcinoma A549 xenograft model...
December 5, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27902413/methanosarcina-acetivorans-utilizes-a-single-nadph-dependent-thioredoxin-system-and-contains-additional-thioredoxin-homologs-with-distinct-functions
#20
Addison C McCarver, Faith H Lessner, Jose M Soroeta, Daniel J Lessner
The thioredoxin system plays a central role in the intracellular redox maintenance in the majority of cells. The canonical system is comprised of an NADPH-dependent thioredoxin reductase (TrxR) that reduces the disulfide reductase thioredoxin (Trx). Although Trx is encoded in almost all sequenced genomes of methanogens, its incorporation into their unique physiology is not well understood. Methanosarcina acetivorans contains a single TrxR (MaTrxR) and seven Trx (MaTrx1-7) homologs. We previously showed that MaTrxR and at least MaTrx7 comprise a functional NADPH-dependent thioredoxin system...
November 29, 2016: Microbiology
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