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https://www.readbyqxmd.com/read/27923281/nuclear-factor-erythroid-derived-2-like-2-and-thioredoxin-1-in-atherosclerosis-and-ischemia-reperfusion-injury-in-the-heart
#1
Philipp Jakobs, Vlad Serbulea, Norbert Leitinger, Anna Eckers, Judith Haendeler
Significance Redox signaling is one of the key elements involved in cardiovascular diseases. Two important molecules are the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and the oxidoreductase Thioredoxin-1 (Trx-1). Recent Advances During the last years, a lot of studies investigated Nrf2 and Trx-1 as protective proteins in cardiovascular disorders. Moreover, post-translational modifications of those molecules were identified which play an important role in the cardiovascular system...
December 6, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27923109/generation-of-domain-specific-monoclonal-antibodies-against-human-glutaredoxin3
#2
Xin Dai, Yanqing Li, Xiaohong Sun, Kai Cai, Qinwen Mao, Haibin Xia
Human Glutaredoxin3 (hGLRX3), which encodes a 37.4 kDa protein, possesses an N-terminal Trx homology domain followed by two tandem repeats of Grx domains. GLRX3 is expressed in many tissues and plays important roles in iron metabolism, antioxidant effect, cell proliferation and development, regulation of immune reaction, and tumorigenesis. The mechanisms underlying the biological function of GLRX3 are still not clear. To facilitate the functional research of GLRX3, in this study, monoclonal antibodies (MAbs) against hGLRX3 were produced by using purified prokaryotic recombinant 6His-hGLRX3 fusion protein as the immunogen...
December 6, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27914046/production-of-computationally-designed-small-soluble-and-membrane-proteins-cloning-expression-and-purification
#3
Barsa Tripathy, Rudresh Acharya
This book chapter focuses on expression and purification of computationally designed small soluble proteins and membrane proteins that are ordinarily difficult to express in good amounts for experiments. Over-expression of such proteins can be achieved by using the solubility tag such as maltose binding protein (MBP), Thioredoxin (Trx), and Gultathione-S-transferase (GST) fused to the protein of interest. Here, we describe and provide the protocols for cloning, expression and purification of such proteins using the solubility tag...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27902413/methanosarcina-acetivorans-utilizes-a-single-nadph-dependent-thioredoxin-system-and-contains-additional-thioredoxin-homologs-with-distinct-functions
#4
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
https://www.readbyqxmd.com/read/27872753/multifunctional-thioredoxin-like-protein-from-the-gastrointestinal-parasitic-nematodes-strongyloides-ratti-and-trichuris-suis-affects-mucosal-homeostasis
#5
Dana Ditgen, Emmanuela M Anandarajah, Jan Hansmann, Dominic Winter, Guido Schramm, Klaus D Erttmann, Eva Liebau, Norbert W Brattig
The cellular redox state is important for the regulation of multiple functions and is essential for the maintenance of cellular homeostasis and antioxidant defense. In the excretory/secretory (E/S) products of Strongyloides ratti and Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were identified. To characterize the antioxidant Trx-lp and its interaction with the parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and recombinantly expressed. The primary antioxidative activity was assured by reduction of insulin and IgM...
2016: Journal of Parasitology Research
https://www.readbyqxmd.com/read/27869186/regulation-of-anticancer-styrylpyrone-biosynthesis-in-the-medicinal-mushroom-inonotus-obliquus-requires-thioredoxin-mediated-transnitrosylation-of-s-nitrosoglutathione-reductase
#6
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
https://www.readbyqxmd.com/read/27869172/a-redox-state-dictated-signalling-pathway-deciphers-the-malignant-cell-specificity-of-cd40-mediated-apoptosis
#7
C J Dunnill, K Ibraheem, A Mohamed, J Southgate, N T Georgopoulos
CD40, a member of the tumour necrosis factor receptor (TNFR) superfamily, has the capacity to cause extensive apoptosis in carcinoma cells, while sparing normal epithelial cells. Yet, apoptosis is only achieved by membrane-presented CD40 ligand (mCD40L), as soluble receptor agonists are but weakly pro-apoptotic. Here, for the first time we have identified the precise signalling cascade underpinning mCD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not MKK7) activation and JNK/AP-1 induction, leading to a Bak- and Bax-dependent mitochondrial apoptosis pathway...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27865002/gold-i-nhc-complexes-antiproliferative-activity-cellular-uptake-inhibition-of-mammalian-and-bacterial-thioredoxin-reductases-and-gram-positive-directed-antibacterial-effects
#8
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
https://www.readbyqxmd.com/read/27832995/protective-effect-of-sophoraflavanone-g-on-streptozotocin-stz-induced-inflammation-in-diabetic-rats
#9
Hanqing Wang, Li Chen, Liming Zhang, Xiaojuan Gao, Yinghua Wang, Tao Weiwei
The present study was designed to investigate the protective effect of Sophoraflavanone G (SG) on streptozotocin (STZ)-induced diabetic rats. The rats were intraperitoneally injected with STZ (35mg/kg). 7days later, the rats were intragastrically administered with Metformin (MET, 150mg/kg), SG (20mg/kg) or SG (40mg/kg) once daily for consecutive 30 days. The animals were anaesthetized, the blood and liver samples were also collected for further assay. SG significantly decreased the serum levels of glucose, insulin, aspartate transaminase (AST), alanine aminotransferase (ALT)...
November 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27831972/the-role-of-thioredoxin-1-in-suppression-sepsis-through-inhibiting-mitochonrial-induced-apoptosis-in-spleen
#10
Guobing Chen, Xiang Li, Mengbing Huang, Xiaoshuang Zhou, Ye Li, Xiaoqin Mao, Jie Bai
Sepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum mediated inflammation involved in lung in a model of experimental sepsis. However, its effect on mitochondrial -mediated apoptosis in spleen has not been reported. We studied whether Trx-1 could prevent spleen cells apoptosis in sepsis...
November 9, 2016: Shock
https://www.readbyqxmd.com/read/27812538/proproliferative-and-antiapoptotic-action-of-exogenously-introduced-yap-in-pancreatic-%C3%AE-cells
#11
Ting Yuan, Sahar Rafizadeh, Zahra Azizi, Blaz Lupse, Kanaka Durga Devi Gorrepati, Sushil Awal, Jose Oberholzer, Kathrin Maedler, Amin Ardestani
Loss of functional pancreatic β cells is a hallmark of both type 1 and 2 diabetes. Identifying the pathways that promote β cell proliferation and/or block β cell apoptosis is a potential strategy for diabetes therapy. The transcriptional coactivator Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, is a key regulator of organ size and tissue homeostasis by modulating cell proliferation and apoptosis. YAP is not expressed in mature primary human and mouse β cells. We aimed to identify whether reexpression of a constitutively active form of YAP promotes β cell proliferation/survival...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27809355/aliskiren-protects-against-myocardial-ischemia-reperfusion-injury-via-an-endothelial-nitric-oxide-synthase-dependent-manner
#12
Yu Chen, Guoliang Meng, Wenli Bai, Yan Ma, Liping Xie, Naila Altaf, Yanning Qian, Yi Han, Yong Ji
Aliskiren, a direct renin inhibitor, was shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS(-/-) ) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg/day of aliskiren...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27777067/securinine-disturbs-redox-homeostasis-and-elicits-oxidative-stress-mediated-apoptosis-via-targeting-thioredoxin-reductase
#13
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
https://www.readbyqxmd.com/read/27753144/melatonin-rescues-cardiac-thioredoxin-system-during-ischemia-reperfusion-injury-in-acute-hyperglycemic-state-by-restoring-notch1-hes1-akt-signaling-in-a-membrane-receptor-dependent-manner
#14
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
https://www.readbyqxmd.com/read/27733046/targeting-of-the-glutathione-thioredoxin-and-nrf2-antioxidant-systems-in-head-and-neck-cancer
#15
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
https://www.readbyqxmd.com/read/27717462/plastidic-p2-glucose-6p-dehydrogenase-from-poplar-is-modulated-by-thioredoxin-m-type-distinct-roles-of-cysteine-residues-in-redox-regulation-and-nadph-inhibition
#16
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
https://www.readbyqxmd.com/read/27716777/thioredoxin-inhibitors-attenuate-platelet-function-and-thrombus-formation
#17
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
https://www.readbyqxmd.com/read/27698473/apocynin-and-nox2-regulate-nf-%C3%AE%C2%BAb-by-modifying-thioredoxin-1-redox-state
#18
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
https://www.readbyqxmd.com/read/27693599/pleiotropic-properties-of-ask1
#19
REVIEW
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
https://www.readbyqxmd.com/read/27665998/thioredoxin-and-redox-signaling-roles-of-the-thioredoxin-system-in-control-of-cell-fate
#20
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
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