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Thioredoxin reductase

R McCall, M Miles, P Lascuna, B Burney, Z Patel, K J Sidoran, V Sittaramane, J Kocerha, D A Grossie, J L Sessler, K Arumugam, J F Arambula
To achieve a systems-based approach to targeting the antioxidant pathway, 1,4-naphthoquinone annulated N-heterocyclic carbene (NHC) [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] [silver(i) dichloride] ( 1 ), [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] chloride ( 2 ), and 1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i) chloride ( 3 )) were designed, synthesized, and tested for biological activity in a series of human cancer cell lines. The solution phase of complexes 1-3 were assigned using several spectroscopy techniques, including NMR spectroscopic analysis...
September 1, 2017: Chemical Science
Colin G Miller, Arne Holmgren, Elias S J Arnér, Edward E Schmidt
Over the past seven decades, research on autotrophic and heterotrophic model organisms has defined how the flow of electrons ("reducing power") from high-energy inorganic sources, through biological systems, to low-energy inorganic products like water, powers all of Life's processes. Universally, an initial major biological recipient of these electrons is nicotinamide adenine dinucleotide-phosphate, which thereby transits from an oxidized state (NADP+ ) to a reduced state (NADPH). A portion of this reducing power is then distributed via the cellular NADPH-dependent disulfide reductase systems as sequential reductions of disulfide bonds...
March 30, 2018: Free Radical Biology & Medicine
Chen Zhang, Catherine Hemmert, Heinz Gornitzka, Olivier Cuvillier, Ming Zhang, Raymond Wai-Yin Sun
A structurally diverse library of fourteen gold(I) cationic bis(NHC) and neutral mono (NHC) complexes (whereas NHC = N-heterocyclic carbene) has been synthesized and characterized in this work. Four of them are new cationic gold(I) complexes containing functionalized NHCs with their X-ray structures presented. All of these complexes have been investigated for their anti-cancer activities in four cancer cell lines including a cisplatin-resistant variant and compared to a non-cancerous cell line. Among them, seven cationic gold(I) complexes were found to display high and specific cytotoxic activities towards cancer cells...
March 30, 2018: ChemMedChem
Mengnan Chen, Jianshe Zhang, Xiaoze Xie, Changwen Wu
Thioredoxin(Trx)with a redox-active disulfide/dithiol in the active site, is an ubiquitous disulfide reductase majorly responsible for maintaining the balance of reactive oxygen species. In this study, the complete thioredoxin-like protein 1 (designated as LcTrx) was cloned from large yellow croaker Larimichthys crocea through rapid amplification of cDNA ends. The full-length cDNA of LcTrx was 1295 bp in length containing a 131 bp 5' untranslated region (UTR) ,a 3'UTR of 294bp with a poly (A) tail, and an 870 bp open reading frame (ORF) encoding a polypeptide of 289 amino acids...
March 27, 2018: Fish & Shellfish Immunology
Changgong Wu, Tong Liu, Yan Wang, Lin Yan, Chuanlong Cui, Annie Beuve, Hong Li
S-Nitrosation is a key posttranslational modification in regulating proteins in both normal physiology and diverse human diseases. To identify novel therapies for human diseases linked to oxidative and nitrosative stress, understanding how cells control S-nitrosation specificity could be critical. Among the enzymes known to control S-nitrosation of proteins, thioredoxin 1 (Trx1), a conserved disulfide reductase, transnitrosates and denitrosates distinct sets of target proteins. To recognize the function of Trx1 in both normal and dysfunctional cells, S-nitrosation targets of Trx1 in different cells need to be identified...
2018: Methods in Molecular Biology
Valeria Scalcon, Alberto Bindoli, Maria Pia Rigobello
Thioredoxin reductase 2 (TrxR2) is a key component of the mitochondrial thioredoxin system able to transfer electrons to peroxiredoxin 3 (Prx3) in a reaction mediated by thioredoxin 2 (Trx2). In this way, both the level of hydrogen peroxide and thiol redox state are modulated. TrxR2 is often overexpressed in cancer cells conferring apoptosis resistance. Due to their exposed flexible arm containing selenocysteine, both cytosolic and mitochondrial TrxRs are inhibited by a large number of molecules. The various classes of inhibitors are listed and the molecules acting specifically on TrxR2 are extensively described...
March 26, 2018: Free Radical Biology & Medicine
Wen Zhu, Xue-Rui Wang, Si-Qi Du, Chao-Qun Yan, Na-Na Yang, Lu-Lu Lin, Guang-Xia Shi, Cun-Zhi Liu
Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that effects cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) were involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model...
March 25, 2018: Neuroscience
N T Moldogazieva, I M Mokhosoev, N B Feldman, S V Lutsenko
Over the last decade, a dual character of cell response to oxidative stress, eustress vs. distress, has become increasingly recognized. A growing body of evidence indicates that under physiological conditions, low concentrations of reactive oxygen and nitrogen species (RONS) maintained by the activity of endogenous antioxidant system (AOS) allow reversible oxidative/nitrosative modifications of key redox-sensitive residues in regulatory proteins. The reversibility of redox modifications such as Cys S-sulfenylation/S-glutathionylation/S-nitrosylation/S-persulfidation and disulfide bond formation, or Tyr nitration, which occur through electrophilic attack of RONS to nucleophilic groups in amino acid residues provides redox switches in the activities of signaling proteins...
March 28, 2018: Free Radical Research
Michael J Maroney, Robert J Hondal
This review highlights the contributions of Jean Chaudière to the field of selenium biochemistry. Chaudière was the first to recognize that one of the main reasons that selenium in the form of selenocysteine is used in proteins is due to the fact that it strongly resists permanent oxidation. The foundations for this important concept was laid down by Al Tappel in the 1960's and even before by others. The concept of oxygen tolerance first recognized in the study of glutathione peroxidase was further advanced and refined by those studying [NiFeSe]-hydrogenases, selenosubtilisin, and thioredoxin reductase...
March 24, 2018: Free Radical Biology & Medicine
Xinming Li, Yanan Hou, Xianke Meng, Chunpo Ge, Huilong Ma, Jin Li, Jianguo Fang
Elevated reactive oxygen species and antioxidant defense systems have been recognized as one of the hallmarks of cancer cells. As a major regulator of the cellular redox homeostasis, the selenoprotein thioredoxin reductase (TrxR) is increasingly considered as a promising target for anticancer drug development. The current approach to inhibit TrxR predominantly relies on the modification of the selenocysteine residue in the C-terminal active site of the enzyme, which is hard to avoid the off-target effects. By conjugating the anticancer drug gemcitabine with a 1, 2-dithiolane scaffold, we disclosed here an unprecedented prodrug strategy that achieves a specific release of gemcitabine by TrxR in cells...
March 26, 2018: Angewandte Chemie
Karessa White, Mi-Jung Kim, Chul Han, Hyo-Jin Park, Dalian Ding, Kevin Boyd, Logan Walker, Paul Linser, Zaimary Meneses, Cole Slade, Jonathan Hirst, Katherine Santostefano, Naohiro Terada, Takuya Miyakawa, Masaru Tanokura, Richard Salvi, Shinichi Someya
Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2-/- mice...
March 22, 2018: Scientific Reports
Lucia A Seale, Herena Y Ha, Ann C Hashimoto, Marla J Berry
Selenoprotein P (SelenoP) functions as a plasma transporter of selenium (Se) from liver to other tissues via incorporation into multiple selenocysteine (Sec) residues. Selenocysteine lyase (Scly) is an intracellular enzyme that decomposes Sec into selenide, providing Se for the synthesis of new selenoproteins. Both SelenoP and Scly are mostly produced by the liver. Previous studies demonstrated that male mice lacking SelenoP (SelenoP KO) or Scly (Scly KO) had increased or decreased total hepatic Se, respectively...
March 19, 2018: Free Radical Biology & Medicine
Jingfei Zhang, Kai Wen Bai, Jintian He, Yu Niu, Yuan Lu, Lili Zhang, Tian Wang
The aim of this study was to investigate the effects of dietary curcumin supplementation on the performance, mitochondrial redox system, mitochondrial DNA (mtDNA) integrity, and antioxidant-related gene expression in the liver of broiler chickens after heat stress treatment. At day 21, a total of 400 Arbor Acres broiler chickens with similar body weight (BW) were divided into 5 groups with 8 replicates per group and then reared either at a normal temperature (22 ± 1 °C) or at a high ambient temperature (34 ± 1 °C for 8 h and 22 ± 1 °C for the remaining time) for 20 d...
March 16, 2018: Journal of Animal Science
Beena Negi, Prija Poonan, Mohammad Fawad Ansari, Deepak Kumar, Sakshi Aggarwal, Ramandeep Singh, Amir Azam, Diwan S Rawat
A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50  = 0.12-0.35 μM) than the reference drug metronidazole (IC50  = 1.79 μM). The most active compounds were found to be non-toxic (up to 50 μM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action...
March 13, 2018: European Journal of Medicinal Chemistry
Paula K Bautista-Niño, Marien van der Stel, Wendy W Batenburg, René de Vries, Anton J M Roks, A H Jan Danser
Protein kinase G (PKG) Iα mediates the cyclic guanosine monophosphate-mediated vasodilatory effects induced by NO. Endothelium-derived hyperpolarizing factors (EDHFs), like H2 O2 can activate PKGIα in a cyclic guanosine monophosphate-independent manner, but whether this is true for all EDHFs (e.g., S-nitrosothiols) is unknown. Here, we investigated the contribution of PKGIα to bradykinin-, H2 O2 -, L-S-nitrosocysteine-, and light-induced relaxation in porcine coronary arteries, making use of the fact that thioredoxin reductase inhibition with auranofin or 1-chloro-2,4-dinitrobenzene potentiates PKGIα...
March 14, 2018: European Journal of Pharmacology
Donatella Pietraforte, Eleonora Paulicelli, Clarice Patrono, Lucrezia Gambardella, Giuseppe Scorza, Antonella Testa, Paola Fattibene
Reactive oxygen species (ROS) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (IR) with all critical cellular components, such as proteins, lipids, and nucleic acids. The derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. To understand how cell damage is induced, we studied the oxidative events occurring immediately after cell irradiation by analysing the fate of IR-derived ROS, the intracellular oxidative damage, and the modification of redox environment accumulating in Chinese hamster ovary (CHO) within 1 h after cell irradiation (dose range 0-10 Gy)...
March 16, 2018: Free Radical Research
Jagpreet Singh Sidhu, Ashutosh Singh, Neha Garg, Navneet Kaur, Narinder Singh
Thioredoxin Reductase (TrxR) is a redox regulating enzyme which is predestined for the maintenance of redox homeostasis of mammalian cells. However, the elevated level of TrxR is associated with the progress of various types of tumors and therefore, this is a significant target for the detection of cancer cells. Herein, an easily engineered 'Turn ON' fluorescent sensor probe has been synthesized for the detection of TrxR and cell imaging using carbon dots. The emission intensity of fCDs on complexation with Cu2+ ions was drastically quenched...
March 15, 2018: Analyst
Parismita Kalita, Harish Shukla, Rohit Shukla, Timir Tripathi
The thiol-disulfide redox metabolism in platyhelminth parasites depends entirely on a single selenocysteine (Sec) containing flavoenzyme, thioredoxin glutathione reductase (TGR) that links the classical thioredoxin (Trx) and glutathione (GSH) systems. In the present study, we investigated the catalytic and structural properties of different variants of Fasciola gigantica TGR to understand the role of Sec. The recombinant full-length Sec containing TGR (FgTGRsec), TGR without Sec (FgTGR) and TGRsec without the N-terminal glutaredoxin (Grx) domain (∆NTD-FgTGRsec) were purified to homogeneity...
March 8, 2018: Biochimica et Biophysica Acta
Tina Markus, David Ley, Stefan R Hansson, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. RESULTS: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD...
March 9, 2018: BMC Neuroscience
ZunGuo Du, XiuJuan Liu, Tao Chen, WenChao Gao, ZhengMing Wu, ZhiQian Hu, Dong Wei, ChunFang Gao, QingQuan Li
A major obstacle for successful management of patients with colorectal carcinoma (CRC) is resistance to anti-cancer cytotoxic treatments. Here, we identified a mechanism of multidrug resistance in wild-type Kras CRCs based on the survival of a cell subpopulation characterized by Sirt5 expression. Sirt5+ cells in wild-type Kras CRCs are resistant to either chemotherapeutic agents or cetuximab and serve as a reservoir for recurrence. Sirt5 demalonylates and inactivates succinate dehydrogenase complex subunit A (SDHA), leading to an accumulation of the oncometabolite succinate...
March 6, 2018: Cell Reports
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