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Thioredoxin reductase

Elias S J Arnér
The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, encoded in human by TXNRD1) is implied to have several different roles in relation to cancer. Its physiologic functions may protect normal cells from carcinogenesis, but may also promote cancer progression if carcinogenesis nonetheless occurs. With distinct links to Nrf2 signaling, ribonucleotide reductase-dependent production of deoxyribonucleotides and its support of several antioxidant systems counteracting oxidative stress, the metabolic pathways regulated, and affected by TrxR1, are altogether of crucial importance in cancer...
2017: Advances in Cancer Research
Rohit Shukla, Harish Shukla, Parismita Kalita, Timir Tripathi
Fascioliasis is caused by the helminth parasites of genus Fasciola. Thioredoxin glutathione reductase (TGR) is an important enzyme in parasitic helminths and plays an indispensable role in its redox biology. In the present study, we conducted a structure-based virtual screening of natural compounds against the Fasciola gigantica TGR (FgTGR). The compounds were docked against FgTGR in four sequential docking modes. The screened ligands were further assessed for Lipinski and ADMET prediction so as to evaluate drug proficiency and likeness property...
October 20, 2017: Journal of Cellular Biochemistry
Weishan Zhuge, Ruijie Chen, Katanaev Vladimir, Xidan Dong, Khan Zia, Xiangwei Sun, Xuanxuan Dai, Miao Bao, Xian Shen, Guang Liang
Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells...
October 13, 2017: Cancer Letters
Odile Valette, Tam T T Tran, Christine Cavazza, Elodie Caudeville, Gaël Brasseur, Alain Dolla, Emmanuel Talla, Laetitia Pieulle
Thioredoxin reductase (TR) regulates the intracellular redox environment by reducing thioredoxin (Trx). In anaerobes, recent findings indicate that the Trx redox network is implicated in the global redox regulation of metabolism but also actively participates in protecting cells against O2. In the anaerobe Desulfovibrio vulgaris Hildenborough (DvH), there is an intriguing redundancy of the Trx system which includes a classical system using NADPH as electron source, a non-canonical system using NADH and an isolated TR (DvTRi)...
2017: Frontiers in Microbiology
E Gasparino, A P Del Vesco, A S Khatlab, V Zancanela, D O Grieser, S C C Silva
We evaluated the effects of heat stress (HS) and methionine supplementation on biological markers of stress and expression of the genes for superoxide dismutase (SOD), thioredoxin (TRx), thioredoxin reductase 1 (TRxR1) and methionine sulfoxide reductase A (MsrA) in broilers aged 1 to 21 or 22 to 42 days. The broilers were divided into two treatments, one with the recommended level of methionine supplementation (MS, supplementation of dl-2-hydroxy-4-methylthiobutanoic acid (dl-HMTBA)) and one without methionine supplementation (MD)...
October 12, 2017: Animal: An International Journal of Animal Bioscience
Yongmei Guo, Sumei Yan, Jian Gong, Lu Jin, Binlin Shi
To elucidate the effect of selenium (Se) on antioxidant function of mammary glands in dairy cows and the underlying mechanism, an experiment was conducted using a single-factor completely randomized design study. Bovine mammary epithelial cells (BMECs) were randomly divided into four groups: control, Se treatment, 2,4-dinitrochlorobenzene (DNCB) inhibition, and Se prevention. Treatment of BMECs with Se was found to significantly reverse decreased cell proliferation and the expression of thioredoxin reductase (TrxR) after DNCB exposure...
October 11, 2017: Biological Trace Element Research
Junmin Zhang, Yaping Liu, Danfeng Shi, Guodong Hu, Baoxin Zhang, Xinming Li, Ruijuan Liu, Xiao Han, Xiaojun Yao, Jianguo Fang
Mammalian thioredoxin reductase (TrxR) enzymes play a crucial role in regulating multiple redox-based signaling pathways and have attracted increasing attention as promising anticancer drug targets. We report here the synthesis of a panel of naphthazarin derivatives and discovery of 2-methyl-5,8-dihydroxy-1,4-naphthoquinone (3, 2-methylnaphthazarin) as a potent cytotoxic agent with a submicromolar half maximal inhibitory concentration to the human promyelocytic leukemia HL-60 cells. Mechanism studies reveal that the compound selectively inhibits TrxR to induce oxidative stress-mediated apoptosis of HL-60 cells...
September 19, 2017: European Journal of Medicinal Chemistry
Leila Tabrizi, Hossein Chiniforoshan
New multinuclear gold(iii), palladium(ii) pincer complexes containing bis(diphenylphosphino) ferrocene/non-ferrocene ligands of formula [(L)Au(μ(2)-η(2)-CS3)Pd(dppf)](PF6)2, 1, and [(L)Au(μ(2)-η(2)-CS3)Pd(dppe)](PF6)2, 2 (HL = 5-methoxy-1,3-bis (1-methyl-1H-benzo[d]imidazol-2-yl)benzene, dppf = 1,1'-bis(diphenylphosphino)ferrocene, and dppe = bis(diphenylphosphino)ethane) have been synthesized and fully characterized. Both complexes are more cytotoxic to a number of human cancer cell lines than cisplatin...
October 6, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Inès Karmous, Rafael Trevisan, Ezzeddine El Ferjani, Abdelilah Chaoui, David Sheehan
In agriculture, heavy metal contamination of soil interferes with processes associated with plant growth, development and productivity. Here, we describe oxidative and redox changes, and deleterious injury within cotyledons and seedlings caused by exposure of germinating (Phaseolus vulgaris L. var. soisson nain hâtif) seeds to copper (Cu). Cu induced a marked delay in seedling growth, and was associated with biochemical disturbances in terms of intracellular oxidative status, redox regulation and energy metabolism...
2017: PloS One
Karoline Johanna Habermann, Leon Grünewald, Sjoerd van Wijk, Simone Fulda
Rhabdomyosarcoma (RMS) cells have recently been reported to be sensitive to oxidative stress. Therefore, we investigated whether concomitant inhibition of the two main antioxidant defense pathways, that is, the thioredoxin (TRX) and the glutathione (GSH) systems, presents a new strategy to trigger cell death in RMS. In this study, we discover that GSH-depleting agents, i.e. γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine (BSO) or the cystine/glutamate antiporter inhibitor erastin (ERA), synergize with thioredoxin reductase (TrxR) inhibitor auranofin (AUR) to induce cell death in RMS cells...
October 5, 2017: Cell Death & Disease
Christoph Loderer, Venkateswara Rao Jonna, Mikael Crona, Inna Rozman Grinberg, Margareta Sahlin, Anders Hofer, Daniel Lundin, Britt-Marie Sjöberg
Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to the corresponding deoxyribonucleotides, used in DNA synthesis and repair. Two different mechanisms help deliver the required electrons to the RNR active site. Formate can be used as reductant directly in the active site, or gluta- or thioredoxins reduce a C-terminal cysteine pair, which then delivers the electrons to the active site. Here, we characterized a novel cysteine-rich C-terminal domain (CRD), which is present in most class II RNRs found in microbes...
October 2, 2017: Journal of Biological Chemistry
Xiaoqing Zheng, Weiwei Ma, Ruoxuan Sun, Hanwei Yin, Fei Lin, Yuxi Liu, Wei Xu, Huihui Zeng
Hepatocellular carcinoma (HCC) accounts for most of primary liver cancer, of which five-year survival rate remains low and chemoprevention has become a strategy to reduce disease burden of HCC. We aim to explore the in vivo chemopreventive effect of an organoselenium-containing compound butaselen (BS) against hepatocarcinogenesis and its underlying mechanisms. Pre- and sustained BS treatment (9, 18 and 36mg/Kg BS) could dose-dependently inhibit chronic hepatic inflammation, fibrosis, cirrhosis and HCC on murine models with 24 weeks treatment scheme...
September 22, 2017: Redox Biology
Jie Yang, Sattar Hamid, Qi Liu, Jingzeng Cai, Shiwen Xu, Ziwei Zhang
Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in myocardium. The aim of this study was to clarify the effect of Txn low expression on 25 selenoproteins in chicken cardiomyocytes. We developed a Se-deficient model (0.033mg/kg) and Txn knock down cardiomyocytes model (siRNA) studies. Western Blot, Quantitative Real-time PCR (qPCR) were performed, and correlation analysis, heat map were used for further analysis. Both low expression of Txn models are significantly decreased (P<0...
September 4, 2017: Journal of Inorganic Biochemistry
Filip Radenkovic, Olivia Holland, Jessica J Vanderlelie, Anthony V Perkins
Auranofin is a thiol-reactive gold (I)-containing compound with potential asa chemotherapeutic. Auranofin has the capacity to selectively inhibit endogenous antioxidant enzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx), resulting in oxidative stress and the initiation of a pro-apoptotic cascade. The effect of Auranofin exposure on TrxR and GPx, and the potential for cellular protection through selenium supplementation was examined in the non-cancerous human cell line Swan-71. Auranofin exposure resulted in a concentration dependent differential inhibition of selenoprotein antioxidants...
September 22, 2017: Biochemical Pharmacology
Mahaveer Prasad Purohit, Neeraj Kumar Verma, Aditya Kumar Kar, Amrita Singh, Debabrata Ghosh, Satyakam Patnaik
Increasing evidences suggest Selenium nanoparticles (Se NPs) as potential cancer therapeutic agents and emerging drug delivery carriers, yet, the molecular mechanism of their anticancer activity still remains unclear. Recent studies indicate, Thioredoxin Reductase (TrxR), a selenoenzyme, as a promising target for anticancer therapy. The present study explored the TrxR inhibition efficacy of Se NPs as a plausible factor impeding tumor growth. Hyaluronic acid (HA) functionalized selenopolymeric nanocarriers (Se@CMHA NPs) were designed wielding chemotherapeutic potential for target specific Doxorubicin (DOX) delivery...
September 25, 2017: ACS Applied Materials & Interfaces
Ratanti Sarkhel, Parvathy Rajan, Ashish Kumar Gupta, Manoj Kumawat, Pranjali Agarwal, Arijit Shome, Manish Mahawar Lalsangpuii
Defending phagocyte generated oxidants is the key for survival of Salmonella Typhimurium (S. Typhimurium) inside the host. Met residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO). Methionine sulfoxide reductase (Msr) can repair Met-SO to Met thus restoring the function(s) of Met-SO containing proteins. Using pull down method we have identified several MsrA interacting proteins in the S. Typhimurium, one of them was malate synthase (MS). MS is an enzyme of glyoxylate cycle. This cycle is essential for survival of S...
September 20, 2017: Biochimica et Biophysica Acta
Yew Kwang Toh, Asha Manikkoth Balakrishna, Malathy Sony Subramanian Manimekalai, Boon Bin Chionh, Ramya Ramaswamy Chettiyan Seetharaman, Frank Eisenhaber, Birgit Eisenhaber, Gerhard Grüber
The ability of the vancomycin-resistant Enterococcus faecalis (V583) to restore redox homeostasis via antioxidant defense mechanism is of importance, and knowledge into this defense is essential to understand its antibiotic-resistance and survival in hosts. The flavoprotein disulfide reductase AhpR, composed of the subunits AhpC and AhpF, represents one such vital part. Circular permutation was found to be a feature of the AhpF protein family. E. faecalis (V583) AhpF (EfAhpF) appears to be a representative of a minor subclass of this family, the typically N-terminal two-fold thioredoxin-like domain (NTD_N/C) is located at the C-terminus, whereas the pyridine nucleotide-disulfide oxidoreductase domain is encoded in the N-terminal part of its sequence...
September 18, 2017: Biochimica et Biophysica Acta
Wenjun Xiao, Li Jiang, Weiyu Wang, Ruyue Wang, Jun Fan
Fusion of solubility-enhancing tag is frequently used for improving soluble production of target protein in Escherichia coli. The Arabidopsis tetraticopeptide domain-containing thioredoxin (TDX) has been documented to exhibit functions of disulfide reductase, foldase chaperone, and holdase chaperone. Here, we identified that fusion of rice TDX with the smaller size increased soluble expression levels of three fluorescent proteins with different fluorophores in the E. coli strain BL21(DE3) or the Rosetta (DE3) strain with coexpression of six rare tRNAs, but decreased conformational quality of certain fluorescent proteins, as comparison with the His6-tagged ones...
September 15, 2017: Journal of Bioscience and Bioengineering
Elias S J Arnér
Thioredoxin reductases are important oxidoreductases that keep the active site disulfide/dithiol motif of thioredoxins reduced using NADPH, thereby supporting many thioredoxin-dependent reductive pathways in cells. Mammalian thioredoxin reductases are selenoproteins that have several additional substrates beyond thioredoxins. This chapter first lists several different assays for measurement of thioredoxin reductase activities, before giving a protocol for a selective evaluation of these activities that can be used in either crude cell lysates as well as with purified enzymes...
2018: Methods in Molecular Biology
Hong Li, Changqing Xu, Quanfeng Li, Xiuxiang Gao, Erkio Sugano, Hiroshi Tomita, Liming Yang, Sa Shi
Mitochondrial oxidative stress is thought to be a key contributor towards the development of diabetic cardiomyopathy. Thioredoxin 2 (Trx2) is a mitochondrial antioxidant that, along with Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), scavenges H₂O₂ and offers protection against oxidative stress. Our previous study showed that TrxR inhibitors resulted in Trx2 oxidation and increased ROS emission from mitochondria. In the present study, we observed that TrxR inhibition also impaired the contractile function of isolated heart...
September 15, 2017: International Journal of Molecular Sciences
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