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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
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Jong-Lyel Roh, Hye Jin Jang, Eun Hye Kim, Daiha Shin
AIMS: The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). RESULTS: At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells...
October 12, 2016: Antioxidants & Redox Signaling
Manuela Cardi, Mirko Zaffagnini, Alessia De Lillo, Daniela Castiglia, Kamel Chibani, José Manuel Gualberto, Nicolas Rouhier, Jean-Pierre Jacquot, Sergio Esposito
A cDNA coding for a plastidic P2-type G6PDH isoform from poplar (Populus tremula x tremuloides) has been used to express and purify to homogeneity the mature recombinant protein with a N-terminus His-tag. The study of the kinetic properties of the recombinant enzyme showed an in vitro redox sensing modulation exerted by reduced DTT. The interaction with thioredoxins (TRXs) was then investigated. Five cysteine to serine variants (C145S - C175S - C183S - C195S - C242S) and a variant with a double substitution for Cys(175) and Cys(183) (C175S/C183S) have been generated, purified and biochemically characterized in order to investigate the specific role(s) of cysteines in terms of redox regulation and NADPH-dependent inhibition...
November 2016: Plant Science: An International Journal of Experimental Plant Biology
Clive Metcalfe, Anjana Ramasubramoni, Giordano Pula, Matthew T Harper, Stuart J Mundell, Carmen H Coxon
Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis...
2016: PloS One
Silvia Cellone Trevelin, Célio Xavier Dos Santos, Raphael Gomes Ferreira, Larissa de Sá Lima, Rangel Leal Silva, Cristoforo Scavone, Rui Curi, José Carlos Alves-Filho, Thiago Mattar Cunha, Pérsio Roxo-Júnior, Maria-Célia Cervi, Francisco Rafael Martins Laurindo, John Stephen Hothersall, Andrew M Cobb, Min Zhang, Aleksandar Ivetic, Ajay M Shah, Lucia Rossetti Lopes, Fernando Queiroz Cunha
The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB...
October 4, 2016: Scientific Reports
Chihiro Sakauchi, Hiroaki Wakatsuki, Hidenori Ichijo, Kazuki Hattori
BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), has the potential to induce cellular apoptosis under various physiological conditions. It has long been suggested that ASK1 is highly sensitive to oxidative stress and contributes substantially to apoptosis. However, recent studies have indicated that ASK1 has pleiotropic roles in living organisms through other mechanisms in addition to apoptosis. SCOPE OF THE REVIEW: This review describes the physiological functions of ASK1 in living organisms, focusing on the regulatory mechanisms of ASK1 activity and its importance in the pathogenesis of various diseases...
September 30, 2016: Biochimica et Biophysica Acta
Atsushi Matsuzawa
Reactive oxygen species (ROS) are not only cytotoxic products from external and internal environment, but also important mediators of redox signaling. Therefore, thioredoxin (Trx) as an antioxidant maintains the balance of the thiol-related redox status, and also plays pivotal roles in the regulation of redox signaling. Trx senses and responds to environmental oxidative stress and ROS generated by cellular respiration, metabolism, and immune response, and then modulates the redox status, function, and activity of its target signaling proteins...
September 22, 2016: Archives of Biochemistry and Biophysics
Katia Lejnev, Lena Khomsky, Krister Bokvist, Shani Mistriel-Zerbib, Tahel Naveh, Thomas Bradley Farb, Jorge Alsina-Fernandez, Daphne Atlas
Impaired insulin signaling and the associated insulin-resistance in liver, adipose tissue, and skeletal muscle, represents a hallmark of the pathogenesis of type 2-diabetes-mellitus. Here we show that in the liver of db/db mice, a murine model of obesity, type 2 diabetes, and dyslipidemia, the elevated activities of mitogen-activated protein kinases (MAPK; ERK1/2 and p38(MAPK)), and Akt/PKB are abolished by rosiglitazone-treatment, which normalizes blood glucose in db/db mice. This is unequivocal evidence of a functional link between the activation of the MAPK specific inflammatory-pathway and high-blood sugar...
September 20, 2016: Free Radical Biology & Medicine
Samuel N Rodman, Jacquelyn M Spence, Tyler J Ronnfeldt, Yueming Zhu, Shane R Solst, Rebecca A O'Neill, Bryan G Allen, Xiangming Guan, Douglas R Spitz, Melissa A Fath
The goal of this study was to determine if depletion of glutathione (GSH) and inhibition of thioredoxin (Trx) reductase (TrxR) activity could enhance radiation responses in human breast cancer stem cells by a mechanism involving thiol-dependent oxidative stress. The following were used to inhibit GSH and Trx metabolism: buthionine sulfoximine (BSO), a GSH synthesis inhibitor; sulfasalazine (SSZ), an inhibitor of xc(-) cysteine/glutamate antiporter; auranofin (Au), a thioredoxin reductase inhibitor; or 2-AAPA, a GSH-reductase inhibitor...
September 19, 2016: Radiation Research
Evelyn Ploetz, Eitan Lerner, Florence Husada, Martin Roelfs, SangYoon Chung, Johannes Hohlbein, Shimon Weiss, Thorben Cordes
Advanced microscopy methods allow obtaining information on (dynamic) conformational changes in biomolecules via measuring a single molecular distance in the structure. It is, however, extremely challenging to capture the full depth of a three-dimensional biochemical state, binding-related structural changes or conformational cross-talk in multi-protein complexes using one-dimensional assays. In this paper we address this fundamental problem by extending the standard molecular ruler based on Förster resonance energy transfer (FRET) into a two-dimensional assay via its combination with protein-induced fluorescence enhancement (PIFE)...
2016: Scientific Reports
Shixiong Cheng, Chenghua Li, Yi Wang, Limeng Yang, Yaqing Chang
As the most important disulfide bond reducates of intracellular oxidordeuctase, thioredoxin (TRX) plays a crucial role in maintaining reducing state of intracellular proteins to normally perform their function. In this study, a cDNA of TRX-like protein gene from Apostichopus japonicus (denoted as AjTRX) was cloned and characterized. The full-length cDNA of AjTRXwas of 1870 bp, consisting of a 5'-UTR of 101 bp, a long 3'-UTR of 887 bp and a 882 bp open reading frame (ORF) encoding a 293 amino acids. The predicted molecular mass and the theoretical PI of the deduced amino acids of AjTRX were 32...
September 14, 2016: Fish & Shellfish Immunology
Zhigang Li, Shuangrong Yuan, Haiyan Jia, Fangyuan Gao, Qian Hu, Dongfa Sun, Hong Luo
Flavodoxin (Fld) plays a pivotal role in photosynthetic microorganisms as an alternative electron carrier flavoprotein under adverse environmental conditions. Cyanobacterial Fld has been demonstrated to be able to substitute ferredoxin (Fd) of higher plants in most electron transfer processes under stressful conditions. We have explored the potential of Fld for use in improving plant stress response in creeping bentgrass (Agrostis stolonifera L.). Overexpression of Fld altered plant growth and development. Most significantly, transgenic (TG) plants exhibited drastically enhanced performance under oxidative, drought and heat stress as well as nitrogen (N) starvation, which was associated with higher water retention and cell membrane integrity than wild type controls, modified expression of heat shock protein (HSP) genes, production of more reduced thioredoxin (Trx), elevated N accumulation and total chlorophyll content as well as up-regulated expression of nitrite reductase and N transporter genes...
September 16, 2016: Plant Biotechnology Journal
Fuwang Wu, Qing Li, Huiling Yan, Dandan Zhang, Guoxiang Jiang, Yueming Jiang, Xuewu Duan
Thioredoxins (Trxs) are small proteins with a conserved redox active site WCGPC and are involved in a wide range of cellular redox processes. However, little information on the role of Trx in regulating low-temperature stress of harvested fruit is available. In this study, three full-length Trx cDNAs, designated MaTrx6, MaTrx9 and MaTrx12, were cloned from banana (Musa acuminata) fruit. Phylogenetic analysis and protein sequence alignments showed that MaTrx6 was grouped to h2 type with a typical active site of WCGPC, whereas MaTrx9 and MaTrx12 were assigned to atypical cys his-rich Trxs (ACHT) and h3 type with atypical active sites of GCAGC and WCSPC, respectively...
2016: International Journal of Molecular Sciences
Muhammad Atteya, Raeesa A Mohamed, Aly M Ahmed, Nayira A Abdel-Baky, Musaad A Alfayez, Hatim D Almalke, Ahmed F El Fouhil
PURPOSE: The present study investigated the effect of lisinopril on experimental autoimmune myocarditis (EAM) in rats, a histologically similar model to human acute myocarditis. ANIMALS AND METHODS: Twenty four, six week-old male Wistar rats were randomly allocated into 4 groups of 6 rats each. Group I received no treatment. Group II received lisinopril at a dose of 15 mg/kg/day suspended in 1 ml of 2% gum acacia daily, from day 1 to day 21. To induce myocarditis, animals of groups III and IV were injected by 1 mg of porcine cardiac myosin on days 1 and 8...
September 7, 2016: Histology and Histopathology
Maryam Sobhani, Ahmad-Reza Taheri, Amir-Hossein Jafarian, Seyed Isaac Hashemy
PURPOSE: Basal cell carcinoma (BCC) is the most prevalent cancer worldwide. Different mechanisms are proposed to be involved in its pathogenesis such as oxidative stress. Oxidative stress, which is the consequence of the disruption of redox balance in favor of oxidants, is involved in the initiation or progression of many tumors. Thioredoxin reductase (TrxR) is a key enzyme of the thioredoxin (Trx) system, containing Trx and TrxR and NADPH, which is one of the main cellular oxidoreductases with an essential role in cellular health and survival through providing and maintaining redox balance...
November 2016: Journal of Cancer Research and Clinical Oncology
Lu Zhao, Yi Feng, Hong Hu, Aiwei Shi, Lei Zhang, Mingxi Wan
Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm(2), 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared...
September 1, 2016: Ultrasound in Medicine & Biology
Dwi Susanti, Usha Loganathan, Biswarup Mukhopadhyay
A recent report suggested that the thioredoxin-dependent metabolic regulation, which is widespread in all domains of life, existed in methanogenic archaea about 3.5 billion years ago. We now show that the respective electron delivery enzyme (thioredoxin reductase, TrxR), although structurally similar to flavin-containing NADPH-dependent TrxRs (NTR), lacked an NADPH-binding site and was dependent on reduced coenzyme F420 (F420H2), a stronger reductant with a mid-point redox potential (E(o')) of -360 mV; E(o') of NAD(P)H is -320 mV...
September 2, 2016: Journal of Biological Chemistry
Salome Kylarova, Dalibor Kosek, Olivia Petrvalska, Katarina Psenakova, Petr Man, Jaroslav Vecer, Petr Herman, Veronika Obsilova, Tomas Obsil
Apoptosis signal-regulating kinase 1 (ASK1, MAP3K5) activates p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase in response to proinflammatory and stress signals. In non-stress conditions, ASK1 is inhibited by association with thioredoxin (TRX) which binds to the TRX-binding domain (ASK1-TBD) at the N-terminus of ASK1. TRX dissociates in response to oxidative stress allowing the ASK1 activation. However, the molecular basis for the ASK1:TRX1 complex dissociation is still not fully understood...
September 2, 2016: FEBS Journal
Jaganathan Subramani, Venkatesh Kundumani-Sridharan, Robert H P Hilgers, Cade Owens, Kumuda C Das
Reversible glutathionylation plays a critical role in protecting protein function in conditions of oxidative stress generally, and for endothelial nitric oxide synthase (eNOS) specifically. Glutathione-dependent glutaredoxin- mediated deglutathionylation of eNOS has been shown to confer protection in a model of heart damage termed ischemia-reperfusion injury, motivating further study of eNOS deglutathionylation in general. In this report we present evidence for an alternative mechanism of deglutathionylation...
September 1, 2016: Journal of Biological Chemistry
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