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Ondrej Kuda, Marie Brezinova, Jan Silhavy, Vladimir Landa, Vaclav Zidek, Chandra Dodia, Franziska Kreuchwig, Marek Vrbacky, Laurence Balas, Thierry Durand, Norbert Hübner, Aron B Fisher, Jan Kopecky, Michal Pravenec
Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising anti-diabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, QTL mapping and correlation analyses in rat BXH/HXB recombinant inbred strains, and response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs.Comprehensive analysis of WAT samples identified ∼160 regioisomers documenting the complexity of this lipid class...
March 16, 2018: Diabetes
Shaohua Yang, Lu Lu Wang, Zhaoyuan Shi, Xiaoqian Ou, Wei Wang, Xue Chen, Guoqing Liu
Considering the high proportion of polyunsaturated fatty acids, the antioxidant defense of chick embryo tissues is vital during the oxidative stress experienced at hatching. In order to better understand the mechanisms of the defense system during chicken embryo development, we detected the activity of antioxidant enzymes during the incubation of chicken embryo. Results showed that the activity of superoxide dismutase (SOD) and (GSH-PX) in livers were higher than those in hearts. Based on these results, liver tissues were used as the follow-up study materials, which were obtained from chicken embryo at day 16 and day 20...
2018: PloS One
Aya Shibata
 Probes that detect specific biological materials are indispensable tools for deepening our understanding of various cellular phenomena. In live cell imaging, the probe must emit fluorescence only when a specific substance is detected. In this paper, we introduce a new probe we developed for live cell imaging. Glutathione S-transferase (GST) activity is higher in tumor cells than in normal cells and is involved in the development of resistance to various anticancer drugs. We previously reported the development of a general strategy for the synthesis of probes for detection of GST enzymes, including fluorogenic, bioluminogenic, and (19)F-NMR probes...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Yanlu Chen, Ruili Feng, Guanghong Luo, Jianjian Guo, Yajiang Wang, Yangyang Sun, Lili Zheng, Tieqiao Wen
Dendritic cell factor 1 (DCF1) is a transmembrane protein that plays important roles in regulating neural stem cell differentiation and dendritic spine formation. Apart from its cytoplasmic functions, DCF1 plays a role in autophagy during the regulation of amyloid precursor proteins. However, the subcellular localization of DCF1 remains unknown. Therefore, in this study, DCF1 tagged with green fluorescent protein was transiently expression in HelaS3 and HEK293T cells. The results showed that DCF1 was widely expressed in different organelles, including the mitochondria, Golgi apparatus, endoplasmic reticulum, endosomes and lysosomes...
October 23, 2017: Biochimie
Huimei Hao, Shanshan Wang
Though important for a variety of medical procedures, general anesthesia is not a problem free. Some anesthetics have been suggested to affect a number of signals, which are associated with memory consolidation and cognition. In the present study, we attempted to investigate the molecular mechanism of anesthesia-regulated processes. We found that under hypothermic condition, anesthetic of isoflurane enhances various signals expression in hippocampus, including Hspd1, Actb, Mgst1, THBS4, Syp, C1QC, Serpine, Plat, and Ngf, which were related to cellular stress, neural plasticity responses, and hippocampal injury...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Marie-Pierre Sanchez, Armelle Govignon-Gion, Pascal Croiseau, Sébastien Fritz, Chris Hozé, Guy Miranda, Patrice Martin, Anne Barbat-Leterrier, Rabia Letaïef, Dominique Rocha, Mickaël Brochard, Mekki Boussaha, Didier Boichard
BACKGROUND: Genome-wide association studies (GWAS) were performed at the sequence level to identify candidate mutations that affect the expression of six major milk proteins in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) dairy cattle. Whey protein (α-lactalbumin and β-lactoglobulin) and casein (αs1, αs2, β, and κ) contents were estimated by mid-infrared (MIR) spectrometry, with medium to high accuracy (0.59 ≤ R(2) ≤ 0.92), for 848,068 test-day milk samples from 156,660 cows in the first three lactations...
September 18, 2017: Genetics, Selection, Evolution: GSE
Ruidong Xiang, Iona M MacLeod, Sunduimijid Bolormaa, Michael E Goddard
While single nucleotide polymorphisms (SNPs) associated with multiple phenotype have been reported, the knowledge of pleiotropy of uncorrelated phenotype is minimal. Principal components (PCs) and uncorrelated Cholesky transformed traits (CT) were constructed using 25 raw traits (RTs) of 2841 dairy bulls. Multi-trait meta-analyses of single-trait genome-wide association studies for RT, PC and CT in bulls were validated in 6821 cows. Most PCs and CTs had substantial estimates of heritability, suggesting that genes affect phenotype via diverse pathways...
August 23, 2017: Scientific Reports
Qie Kuang, Pasi Purhonen, Johan Ålander, Richard Svensson, Veronika Hoogland, Jens Winerdal, Linda Spahiu, Astrid Ottosson-Wadlund, Caroline Jegerschöld, Ralf Morgenstern, Hans Hebert
Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell...
August 11, 2017: Scientific Reports
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...
June 20, 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
Studies support the idea that 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) and glandular epithelium (GE) and the conceptus and proteome of uterine luminal fluid (ULF) during the peri-implantation period of pregnancy. Transcriptome (RNA-sequencing) analysis was conducted in LE and GE isolated from uteri of Day 10, 12, 14, 16, and 20 pregnant sheep by laser capture microdissection...
October 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...
October 2017: 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
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