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Linda Spahiu, Johan Ålander, Astrid Ottosson-Wadlund, Richard Svensson, Carina Lehmer, Richard N Armstrong, Ralf Morgenstern
Microsomal glutathione transferase 1 (MGST1) has a unique ability to be activated, ≤30-fold, by modification with sulfhydryl reagents. MGST1 exhibits one-third-of-the-sites reactivity toward glutathione and hence heterogeneous binding to different active sites in the homotrimer. Limited turnover stopped-flow kinetic measurements of the activated enzyme allowed us to more accurately determine the KD for the "third" low-affinity GSH binding site (1.4 ± 0.3 mM). The rate of thiolate formation, k2 (0.77 ± 0...
June 9, 2017: Biochemistry
Joanna Stafiej, Marta Hałas-Wiśniewska, Magdalena Izdebska, Maciej Gagat, Dariusz Grzanka, Alina Grzanka, Grażyna Malukiewicz
Pseudoexfoliation syndrome (PEX) is an age-associated, sight disorder affecting elastic fibers in the eye and visceral organs but its exact etiology remains unknown. The purpose of the current study was to determine the morphology and ultrastructure of lens epithelial cells (LECs), and to use immunohistochemistry to examine localization of microsomal glutathione S-transferase 1 (MGST1) and clusterin. Anterior lens capsules were obtained from 24 patients (13 PEX and 11 controls) who underwent phacoemulsification...
March 2017: Experimental and Therapeutic Medicine
Wendy N Nembhard, Xinyu Tang, Zhuopei Hu, Stewart MacLeod, Zachary Stowe, Daniel Webber
Objective To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways.Design Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use...
March 6, 2017: BMJ: British Medical Journal
Pei Wu, Yang Liu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
The liver and intestine are susceptible to the oxidative damage which could result in several diseases. Choline deficiency induced oxidative damage in rat liver cells. Thus, this study aimed to investigate the potential molecular mechanisms responsible for choline deficiency-induced oxidative damage. Juvenile Jian carp were fed diets differing in choline content [165 (deficient group), 310, 607, 896, 1167 and 1820 mg/kg diet] respectively for 65 days. Oxidative damage, antioxidant enzyme activities and related gene expressions in the hepatopancreas and intestine were measured...
2017: PloS One
Miyuki Shimoji, Ricardo A Figueroa, Etienne Neve, Danuta Maksel, Gabriela Imreh, Ralf Morgenstern, Einar Hallberg
Microsomal glutathione transferase 1 (MGST1) is a membrane bound enzyme involved in the detoxification of reactive electrophiles and protection of membranes from oxidative stress. The enzyme displays an unusual and broad subcellular distribution with especially high levels in the endoplasmic reticulum (ER) and outer mitochondrial membrane (OMM). Here we examined the molecular basis for this dual distribution. We hypothesized that the amphipathic properties of the first transmembrane segment (TMS), that contains a positively charged lysine (K25), is a central feature guiding dual targeting...
February 2017: Biochimica et Biophysica Acta
Kelsey Brooks, Gregory W Burns, Joao G N Moraes, Thomas E Spencer
Available studies support the idea that the uterine epithelia and their secretions have important biological roles in conceptus survival, elongation and implantation in sheep. The present study evaluated the transcriptome of the uterine luminal epithelium (LE), glandular epithelium (GE) and conceptus, and proteome of the uterine luminal fluid (ULF) during the peri-implantation period of pregnancy. Transcriptome (RNA-sequencing) analysis was conducted on LE and GE isolated from uteri of Day 10, 12, 14, 16, and 20 pregnant sheep by laser capture microdissection...
August 17, 2016: Biology of Reproduction
Matthew F Buas, Qianchuan He, Lisa G Johnson, Lynn Onstad, David M Levine, Aaron P Thrift, Puya Gharahkhani, Claire Palles, Jesper Lagergren, Rebecca C Fitzgerald, Weimin Ye, Carlos Caldas, Nigel C Bird, Nicholas J Shaheen, Leslie Bernstein, Marilie D Gammon, Anna H Wu, Laura J Hardie, Paul D Pharoah, Geoffrey Liu, Prassad Iyer, Douglas A Corley, Harvey A Risch, Wong-Ho Chow, Hans Prenen, Laura Chegwidden, Sharon Love, Stephen Attwood, Paul Moayyedi, David MacDonald, Rebecca Harrison, Peter Watson, Hugh Barr, John deCaestecker, Ian Tomlinson, Janusz Jankowski, David C Whiteman, Stuart MacGregor, Thomas L Vaughan, Margaret M Madeleine
OBJECTIVE: Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA...
August 2, 2016: Gut
Ewa Drozd, Jolanta Krzysztoń-Russjan, Jadwiga Marczewska, Janina Drozd, Irena Bubko, Magda Bielak, Katarzyna Lubelska, Katarzyna Wiktorska, Zdzisław Chilmonczyk, Elżbieta Anuszewska, Beata Gruber-Bzura
Doxorubicin (DOX), one of the most effective anticancer drugs, acts in a variety of ways including DNA damage, enzyme inhibition and generation of reactive oxygen species. Glutathione (GSH) and glutathione-related enzymes including: glutathione peroxidase (GPX), glutathione reductase (GSR) and glutathione S-transferases (GST) may play a role in adaptive detoxification processes in response to the oxidative stress, thus contributing to drug resistance phenotype. In this study, we investigated effects of DOX treatment on expression and activity of GSH-related enzymes and multidrug resistance-associated proteins in cultured human cervical cancer cells displaying different resistance against this drug (HeLa and KB-V1)...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Candelaria Bracalente, Irene L Ibañez, Ariel Berenstein, Cintia Notcovich, María B Cerda, Fabio Klamt, Ariel Chernomoretz, Hebe Durán
Reactive oxygen species (ROS) are implicated in tumor transformation. The antioxidant system (AOS) protects cells from ROS damage. However, it is also hijacked by cancers cells to proliferate within the tumor. Thus, identifying proteins altered by redox imbalance in cancer cells is an attractive prognostic and therapeutic tool. Gene expression microarrays in A375 melanoma cells with different ROS levels after overexpressing catalase were performed. Dissimilar phenotypes by differential compensation to hydrogen peroxide scavenging were generated...
July 5, 2016: Oncotarget
Mathew D Littlejohn, Kathryn Tiplady, Tania A Fink, Klaus Lehnert, Thomas Lopdell, Thomas Johnson, Christine Couldrey, Mike Keehan, Richard G Sherlock, Chad Harland, Andrew Scott, Russell G Snell, Stephen R Davis, Richard J Spelman
The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed. To investigate this QTL in detail, we report genome sequence-based imputation and association mapping in a population of 64,244 taurine cattle...
2016: Scientific Reports
Grace Min Yi Tan, Hui Jing Lim, Tee Cian Yeow, Elaheh Movahed, Chung Yeng Looi, Rishein Gupta, Bernard P Arulanandam, Sazaly Abu Bakar, Negar Shafiei Sabet, Li-Yen Chang, Won Fen Wong
Chlamydia trachomatis is the leading causative agent of bacterial sexually transmitted infections worldwide which can lead to female pelvic inflammatory disease and infertility. A greater understanding of host response during chlamydial infection is essential to design intervention technique to reduce the increasing incidence rate of genital chlamydial infection. In this study, we investigated proteome changes in epithelial cells during C. trachomatis infection by using an isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique coupled with a liquid chromatography-tandem mass spectrometry (LC-MS(3) ) analysis...
May 2016: Proteomics
Marike W van Gisbergen, Marcus Cebula, Jie Zhang, Astrid Ottosson-Wadlund, Ludwig Dubois, Philippe Lambin, Kenneth D Tew, Danyelle M Townsend, Guido R M M Haenen, Marie-José Drittij-Reijnders, Hisao Saneyoshi, Mika Araki, Yuko Shishido, Yoshihiro Ito, Elias S J Arnér, Hiroshi Abe, Ralf Morgenstern, Katarina Johansson
Glutathione transferases (GSTs) are often overexpressed in tumors and frequently correlated to bad prognosis and resistance against a number of different anticancer drugs. To selectively target these cells and to overcome this resistance we previously have developed prodrugs that are derivatives of existing anticancer drugs (e.g., doxorubicin) incorporating a sulfonamide moiety. When cleaved by GSTs, the prodrug releases the cytostatic moiety predominantly in GST overexpressing cells, thus sparing normal cells with moderate enzyme levels...
June 6, 2016: Molecular Pharmaceutics
Katarzyna Pawłowska-Góral, Magdalena Kimsa-Dudek, Agnieszka Synowiec-Wojtarowicz, Joanna Orchel, Marek Glinka, Stanisław Gawron
The available evidence from in vitro and in vivo studies is deemed not sufficient to draw conclusions about the potential health effects of static magnetic field (SMF) exposure. Therefore, the aim of the present study was to determine the influence of static magnetic fields and phloretin on the redox homeostasis of human dermal fibroblasts. Control fibroblasts and fibroblasts treated with phloretin were subjected to the influence of static magnetic fields. Three chambers with static magnetic fields of different intensities (0...
August 2016: Environmental Science and Pollution Research International
Anders E Bilgrau, Steffen Falgreen, Anders Petersen, Malene K Kjeldsen, Julie S Bødker, Hans E Johnsen, Karen Dybkær, Martin Bøgsted
BACKGROUND: Accurate adjustment for the amplification efficiency (AE) is an important part of real-time quantitative polymerase chain reaction (qPCR) experiments. The most commonly used correction strategy is to estimate the AE by dilution experiments and use this as a plug-in when efficiency correcting the Δ Δ C q . Currently, it is recommended to determine the AE with high precision as this plug-in approach does not account for the AE uncertainty, implicitly assuming an infinitely precise AE estimate...
April 11, 2016: BMC Bioinformatics
Zidong Donna Fu, Felcy Pavithra Selwyn, Julia Yue Cui, Curtis D Klaassen
Previous reports on tissue distribution of xenobiotic-processing genes (XPGs) have limitations, because many non-cytochrome P450 phase I enzymes have not been investigated, and one cannot compare the real mRNA abundance of multiple XPGs using conventional quantification methods. Therefore, this study aimed to quantify and compare the mRNA abundance of all major XPGs in the liver and intestine using RNA sequencing. The mRNA profiles of 304 XPGs, including phase I, phase II enzymes, phase II cosubstrate synthetic enzymes, xenobiotic transporters, as well as xenobiotic-related transcription factors, were systematically examined in the liver and various sections of the intestine in adult male C57BL/6J mice...
June 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Bénédicte Allam-Ndoul, Frédéric Guénard, Olivier Barbier, Marie-Claude Vohl
BACKGROUND: Uncontrolled inflammation participates in the development of inflammatory diseases. Beneficial effects of polyunsaturated fatty acids belonging to the n-3 family such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on inflammation have been reported. The present study investigates the basal effects of EPA, DHA and a mixture EPA + DHA on the expression of 10 genes (AKT1, MAPK, NFKB, TNFA, IL1Β, MCP1, ALOX5, PTGS2, MGST1 and NOS2) related to inflammation in unstimulated cultured THP1 macrophages...
April 5, 2016: Lipids in Health and Disease
Sana Bakari, Mehdi Lembrouk, Laura Sourd, Fares Ousalem, François André, Stéphane Orlowski, Marcel Delaforge, Annie Frelet-Barrand
Despite the great importance of human membrane proteins involved in detoxification mechanisms, their wide use for biochemical approaches is still hampered by several technical difficulties considering eukaryotic protein expression in order to obtain the large amounts of protein required for functional and/or structural studies. Lactococcus lactis has emerged recently as an alternative heterologous expression system to Escherichia coli for proteins that are difficult to express. The aim of this work was to check its ability to express mammalian membrane proteins involved in liver detoxification, i...
April 2016: Molecular Biotechnology
Lesley-Ann Raven, Benjamin G Cocks, Kathryn E Kemper, Amanda J Chamberlain, Christy J Vander Jagt, Michael E Goddard, Ben J Hayes
Dairy cattle are an interesting model for gaining insights into the genes responsible for the large variation between and within mammalian species in the protein and fat content of their milk and their milk volume. Large numbers of phenotypes for these traits are available, as well as full genome sequence of key founders of modern dairy cattle populations. In twenty target QTL regions affecting milk production traits, we imputed full genome sequence variant genotypes into a population of 16,721 Holstein and Jersey cattle with excellent phenotypes...
February 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Wei-Dan Jiang, Kai Hu, Jin-Xiu Zhang, Yang Liu, Jun Jiang, Pei Wu, Juan Zhao, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish...
November 28, 2015: British Journal of Nutrition
Ganna Chornokur, Hui-Yi Lin, Jonathan P Tyrer, Kate Lawrenson, Joe Dennis, Ernest K Amankwah, Xiaotao Qu, Ya-Yu Tsai, Heather S L Jim, Zhihua Chen, Ann Y Chen, Jennifer Permuth-Wey, Katja K H Aben, Hoda Anton-Culver, Natalia Antonenkova, Fiona Bruinsma, Elisa V Bandera, Yukie T Bean, Matthias W Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Clareann H Bunker, Ralf Butzow, Ian G Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Andreas du Bois, Evelyn Despierre, Ed Dicks, Jennifer A Doherty, Thilo Dörk, Matthias Dürst, Douglas F Easton, Diana M Eccles, Robert P Edwards, Arif B Ekici, Peter A Fasching, Brooke L Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind Glasspool, Marc T Goodman, Jacek Gronwald, Patricia Harrington, Philipp Harter, Alexander Hein, Florian Heitz, Michelle A T Hildebrandt, Peter Hillemanns, Claus K Hogdall, Estrid Hogdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Bu-Tian Ji, Beth Y Karlan, Linda E Kelemen, Mellissa Kellar, Lambertus A Kiemeney, Camilla Krakstad, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Alice W Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A Levine, Dong Liang, Boon Kiong Lim, Jolanta Lissowska, Karen Lu, Jan Lubinski, Lene Lundvall, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Iain McNeish, Usha Menon, Roger L Milne, Francesmary Modugno, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, Ursula Eilber, Kunle Odunsi, Sara H Olson, Irene Orlow, Sandra Orsulic, Rachel Palmieri Weber, James Paul, Celeste L Pearce, Tanja Pejovic, Liisa M Pelttari, Malcolm C Pike, Elizabeth M Poole, Harvey A Risch, Barry Rosen, Mary Anne Rossing, Joseph H Rothstein, Anja Rudolph, Ingo B Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Eva Schernhammer, Ira Schwaab, Xiao-Ou Shu, Yurii B Shvetsov, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa C Southey, Beata Spiewankiewicz, Lara Sucheston, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Lotte Thomsen, Ingvild L Tangen, Shelley S Tworoger, Anne M van Altena, Robert A Vierkant, Ignace Vergote, Christine S Walsh, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Kristine G Wicklund, Lynne R Wilkens, Anna H Wu, Xifeng Wu, Yin-Ling Woo, Hannah Yang, Wei Zheng, Argyrios Ziogas, Hanis N Hasmad, Andrew Berchuck, Edwin S Iversen, Joellen M Schildkraut, Susan J Ramus, Ellen L Goode, Alvaro N A Monteiro, Simon A Gayther, Steven A Narod, Paul D P Pharoah, Thomas A Sellers, Catherine M Phelan
BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk...
2015: PloS One
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