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Thioredoxin reductase

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
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...
December 5, 2016: Cancer Prevention Research
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
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
Yanxia Zhao, Meihong He, Jianing Ding, Qi Xi, Gary J Loake, Weifa Zheng
The medicinal macrofungus Inonotus obliquus widely utilized as folk medicine in Russia and Baltic countries is a source of phenylpropanoid-derived styrylpyrone polyphenols that can inhibit tumor proliferation. Insights into the regulatory machinery that controls I. obliquus styrylpyrone polyphenol biosynthesis will enable strategies to increase the production of these molecules. Here we show that Thioredoxin (Trx) mediated transnitrosylation of S-nitrosoglutathione reductase (GSNOR) underpins the regulation of styrylpyrone production, driven by nitric oxide (NO) synthesis triggered by P...
November 21, 2016: Scientific Reports
Poulami Mandal, Novina Malviya, M Fátima C Guedes da Silva, Sandeep Singh Dhankhar, C M Nagaraja, Shaikh M Mobin, Suman Mukhopadhyay
Four new ruthenium arene PTA type complexes have been synthesized using substituted picolinamide derivatives as ancillary ligands and characterized by spectroscopic methods. In one of the complexes, the ancillary ligand has shown an unprecedented valence-bond tautomerization in the presence of an ammonium salt to act as a polar neutral donor ligand making the ligand more prone towards substitution. The same compound has shown remarkable antiproliferative activity against three cancer cell lines with GI50 values comparable to Adriamycin, a known therapeutic drug...
November 21, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Seon-Joo Park, Hong Beum Kim, Chunmei Piao, Mi Yeong Kang, Sang-Gon Park, Seok Won Kim, Jung-Hee Lee
Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide reductase family that supplies dNTPs for nuclear and mitochondrial DNA replication and repair. Here, we have identified a mitochondrial thioredoxin reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct interaction between the two, and observed that p53R2 stimulated the enzymatic activity of TrxR in vitro. Moreover, TrxR2 activity was significantly lower in p53R2 knockdown cells, and increased when p53R2 was overexpressed, effects that were independent of p53...
November 17, 2016: Biochemical and Biophysical Research Communications
Claudia Schmidt, Bianka Karge, Rainer Misgeld, Aram Prokop, Raimo Franke, Mark Brönstrup, Ingo Ott
Gold complexes with N-heterocyclic carbene (NHC) ligands represent a promising class of metallodrugs for the treatment of cancer or infectious diseases. In this report, the synthesis and the biological evaluation of halogen-containing (NHC)Au(I)Cl complexes are described. The complexes 1 and 5a-5f displayed good cytotoxic activity against tumor cells, and cellular uptake studies suggested that an intact Au-NHC fragment is essential for the accumulation of high amounts of both the metal and the NHC ligand. However, the bioavailability was negatively affected by serum components of the cell culture media and was influenced by likely transformations of the complex...
November 16, 2016: Chemistry: a European Journal
Ziyan Y Pessetto, Bin Chen, Hani Alturkmani, Stephen Hyter, Colleen A Flynn, Michael Baltezor, Yan Ma, Howard G Rosenthal, Kathleen A Neville, Scott J Weir, Atul J Butte, Andrew K Godwin
The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches...
November 16, 2016: Oncotarget
Chaoran Dong, Lei Zhang, Ruoxuan Sun, Jianying Liu, Hanwei Yin, Xiaoxiao Li, Xiaoqing Zheng, Huihui Zeng
Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme. On the other hand, overexpression of TrxR1 is closely correlated with the initiation of various tumors including breast cancer, though the detailed mechanism remains unclear. Here we investigated the role of TrxR1 in dysplastic transformation of human breast epithelial cell line MCF-10A induced by chronic oxidative stress. Not surprisingly, sustained exposure to H2O2 significantly augmented the expression and activity of TrxR1 in MCF-10A cells...
November 15, 2016: Scientific Reports
Cao Xiaobo, Mourad Majidi, Meng Feng, Ruping Shao, Jing Wang, Yang Zhao, Veerabhadran Baladandayuthapani, Juhee Song, Bingliang Fang, Lin Ji, Reza Mehran, Jack A Roth
Expression of the TUSC2/FUS1 tumor suppressor gene in TUSC2 deficient EGFR wildtype lung cancer cells increased sensitivity to erlotinib. Microarray mRNA expression analysis of TUSC2 inducible lung cancer cells treated with erlotinib uncovered defects in the response to oxidative stress suggesting that increasing reactive oxygen species (ROS) would enhance therapeutic efficacy. Addition of the thioredoxin reductase 1 inhibitor (TXNRD1) auranofin (AF) to NSCLC cells treated with combination of TUSC2 forced expression with erlotinib increased tumor cell apoptosis and inhibited colony formation...
November 15, 2016: Scientific Reports
Alisha Khera, Jessica J Vanderlelie, Olivia Holland, Anthony V Perkins
The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red)...
November 5, 2016: Biological Trace Element Research
Kristin M Allan, Matthew A Loberg, Juliet Chepngeno, Jennifer E Hurtig, Susmit Tripathi, Min Goo Kang, Jonathan K Allotey, Afton H Widdershins, Jennifer M Pilat, Herbert J Sizek, Wesley J Murphy, Matthew R Naticchia, Joseph B David, Kevin A Morano, James D West
A broad range of redox-regulated proteins undergo reversible disulfide bond formation on oxidation-prone cysteine residues. Heightened reactivity of the thiol groups in these cysteines also increases susceptibility to modification by organic electrophiles, a property that can be exploited in the study of redox networks. Here, we explored whether divinyl sulfone (DVSF), a thiol-reactive bifunctional electrophile, cross-links oxidant-sensitive proteins to their putative redox partners in cells. To test this idea, previously identified oxidant targets involved in oxidant defense (namely, peroxiredoxins, methionine sulfoxide reductases, sulfiredoxin, and glutathione peroxidases), metabolism, and proteostasis were monitored for cross-link formation following treatment of Saccharomyces cerevisiae with DVSF...
November 2, 2016: Free Radical Biology & Medicine
Ruixia Dong, Dongxu Wang, Xiaoxiao Wang, Ke Zhang, Pingping Chen, Chung S Yang, Jinsong Zhang
Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system...
October 24, 2016: Redox Biology
Ragini Singh, Ajay Singh Karakoti, William T Self, Sudipta Seal, Sanjay Singh
Cerium oxide nanoparticles (CeNPs) have gathered much attention in the biomedical field due to its unique antioxidant property. It can protect cells and tissues from oxidative stress induced damage due to its auto-regenerative redox cycle. Our study explores the antioxidant and anti-genotoxic behaviour of PEGylated CeNPs towards oxidative insult produced by BSO (Buthionine sulfoximine) in human keratinocytes (HaCaT cells). BSO inhibits the γ-glutamylcysteinesynthetase (γ-GCS) enzyme and thus acts as a glutathione (GSH) depleting agent to modulate the cellular redox potential...
October 28, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Doc Mariano, D de Souza, D F Meinerz, J Allebrandt, A F de Bem, W Hassan, Oed Rodrigues, Jbt da Rocha
Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS...
October 24, 2016: Human & Experimental Toxicology
Junmin Zhang, Juan Yao, Shoujiao Peng, Xinming Li, Jianguo Fang
Thioredoxin reductase (TrxR) and thioredoxin (Trx) are two major components of the thioredoxin system, which plays essential roles in regulating cellular redox signaling. Mammalian TrxRs are essential seleno-flavoenzymes with a conserved penultimate selenocysteine (Sec) residue at the C-terminus, and have attracted considerable interests as promising targets for anticancer drugs. Securinine (SCR), a major active alkaloid lactone from the Chinese herbal medicine Securinega suffruticosa, has been established clinical success in treatment of neurological disorders...
October 21, 2016: Biochimica et Biophysica Acta
Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Detlef Schuppan, Leonard Kaps, Rainer Schobert
Four gold(I) carbene complexes featuring 4-ferrocenyl substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalised lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: via a genuine ferrocene effect and by inhibiting the thioredoxin reductase...
October 20, 2016: Chemistry: a European Journal
Grazyna Nowak, Diana Takacsova Bakajsova, Judit Megyesi
Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of the PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44% and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia...
October 19, 2016: American Journal of Physiology. Renal Physiology
Piotr T Filipczak, Cynthia L Thomas, Wenshu Chen, Andrew Salzman, Jacob D McDonald, Yong Lin, Steven A Belinsky
Tuberous sclerosis complex (TSC) is a genetic multi-organ disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach...
October 18, 2016: Cancer Research
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