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https://www.readbyqxmd.com/read/28923202/dietary-linoleic-acid-and-its-oxidized-metabolites-exacerbate-liver-injury-caused-by-ethanol-via-induction-of-hepatic-proinflammatory-response-in-mice
#1
Dennis R Warner, Huilin Liu, Matthew E Miller, Christopher E Ramsden, Bin Gao, Ariel E Feldstein, Susanne Schuster, Craig J McClain, Irina A Kirpich
Alcoholic liver disease is a major human health problem leading to significant morbidity and mortality in the United States and worldwide. Dietary fat plays an important role in alcoholic liver disease pathogenesis. Herein, we tested the hypothesis that a combination of ethanol and a diet rich in linoleic acid (LA) leads to the increased production of oxidized LA metabolites (OXLAMs), specifically 9- and 13-hydroxyoctadecadienoic acids (HODEs), which contribute to a hepatic proinflammatory response exacerbating liver injury...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28887380/proteomic-signature-reveals-modulation-of-human-macrophage-polarization-and-functions-under-differing-environmental-oxygen-conditions
#2
Magali Court, Graciane Petre, Michèle El-Atifi, Arnaud Millet
Macrophages are innate immune cells which can react to a large number of environmental stimuli thanks to a high degree of plasticity. These cells are involved in a variety of tissue functions in homeostasis, and they play essential roles in pathological contexts. Macrophages’ activation state, which determines their functional orientation, is strongly influenced by the cellular environment. A large body of macrophage literature is devoted to better defining polarizations from a molecular viewpoint. It is now accepted that a multidimensional model of polarization is needed to grasp the broad phenotype repertoire controlled by environmental signals...
September 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28874441/comprehensive-analyses-of-oxidized-phospholipids-using-a-measured-ms-ms-spectra-library
#3
Ryohei Aoyagi, Kazutaka Ikeda, Yosuke Isobe, Makoto Arita
Oxidized phospholipids (OxPLs) are widely held to be associated with various diseases such as arteriosclerosis, diabetes and cancer. To characterize the structure-specific behavior of OxPLs and their physiological relevance, we developed a comprehensive analytical method by establishing a measured MS/MS spectra library of OxPLs . Biogenic OxPLs were prepared by the addition of specific oxidized fatty acids to cultured cells, where they were incorporated into cellular phospholipids, and untargeted lipidomics by LC-quadrupole/time-of-flight (QTOF) MS was applied to collect MS/MS spectra for the OxPLs...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28854238/elastic-network-model-of-learned-maintained-contacts-to-predict-protein-motion
#4
Ines Putz, Oliver Brock
We present a novel elastic network model, lmcENM, to determine protein motion even for localized functional motions that involve substantial changes in the protein's contact topology. Existing elastic network models assume that the contact topology remains unchanged throughout the motion and are thus most appropriate to simulate highly collective function-related movements. lmcENM uses machine learning to differentiate breaking from maintained contacts. We show that lmcENM accurately captures functional transitions unexplained by the classical ENM and three reference ENM variants, while preserving the simplicity of classical ENM...
2017: PloS One
https://www.readbyqxmd.com/read/28851976/linoleic-acid-metabolite-leads-to-steroid-resistant-asthma-features-partially-through-nf-%C3%AE%C2%BAb
#5
Lipsa Panda, Atish Gheware, Rakhshinda Rehman, Manish K Yadav, B S Jayaraj, SubbaRao V Madhunapantula, Padukudru Anand Mahesh, Balaram Ghosh, Anurag Agrawal, Ulaganathan Mabalirajan
Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843180/photoactivation-provides-a-mechanistic-explanation-for-pan-assay-interference-behaviour-of-2-aminopyrroles-in-lipoxygenase-inhibition
#6
Hao Guo, Nikolaos Eleftheriadis, Nataliya Rohr-Udilova, Alexander Dömling, Frank J Dekker
Human 15-lipoxygenase-1 (h-15-LOX-1) is a promising drug target in inflammation and cancer. In this study substitution-oriented screening (SOS) has been used to identify compounds with a 2-aminopyrrole scaffold as inhibitors for h-15-LOX-1. The observed structure activity relationships (SAR) proved to be relatively flat. IC50's for the most potent inhibitor of the series did not surpass 6.3 μM and the enzyme kinetics demonstrated uncompetitive inhibition. Based on this, we hypothesized that the investigated 2-aminopyrroles are pan assay interference compounds (PAINS) with photoactivation via a radical mechanism...
July 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28842399/inhibition-of-12-15-lipoxygenase-protects-against-%C3%AE-cell-oxidative-stress-and-glycemic-deterioration-in-mouse-models-of-type-1-diabetes
#7
Marimar Hernandez-Perez, Gaurav Chopra, Jonathan Fine, Abass M Conteh, Ryan M Anderson, Amelia K Linnemann, Chanelle Benjamin, Jennifer B Nelson, Kara S Benninger, Jerry L Nadler, David J Maloney, Sarah A Tersey, Raghavendra G Mirmira
Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-lipoxygenase (12/15-LOX) is induced in β cells and macrophages during T1D and produces pro-inflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency...
August 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28839250/pharmacological-profile-and-efficiency-in-vivo-of-diflapolin-the-first-dual-inhibitor-of-5-lipoxygenase-activating-protein-and-soluble-epoxide-hydrolase
#8
Ulrike Garscha, Erik Romp, Simona Pace, Antonietta Rossi, Veronika Temml, Daniela Schuster, Stefanie König, Jana Gerstmeier, Stefanie Liening, Markus Werner, Heiner Atze, Sandra Wittmann, Christina Weinigel, Silke Rummler, Gerhard K Scriba, Lidia Sautebin, Oliver Werz
Arachidonic acid (AA) is metabolized to diverse bioactive lipid mediators. Whereas the 5-lipoxygenase-activating protein (FLAP) facilitates AA conversion by 5-lipoxygenase (5-LOX) to pro-inflammatory leukotrienes (LTs), the soluble epoxide hydrolase (sEH) degrades anti-inflammatory epoxyeicosatrienoic acids (EETs). Accordingly, dual FLAP/sEH inhibition might be advantageous drugs for intervention of inflammation. We present the in vivo pharmacological profile and efficiency of N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N'-(3,4-dichlorophenyl)urea (diflapolin) that dually targets FLAP and sEH...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837253/lipoxygenase-mediated-generation-of-lipid-peroxides-enhances-ferroptosis-induced-by-erastin-and-rsl3
#9
Ryosuke Shintoku, Yuta Takigawa, Keiichi Yamada, Chisato Kubota, Yuhei Yoshimoto, Toshiyuki Takeuchi, Ichiro Koshiishi, Seiji Torii
In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOXs) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin- and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds...
August 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28827690/hepatic-overproduction-of-13-hode-due-to-alox15-upregulation-contributes-to-alcohol-induced-liver-injury-in-mice
#10
Wenliang Zhang, Wei Zhong, Qian Sun, Xinguo Sun, Zhanxiang Zhou
Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811867/modulation-of-glutathione-hemostasis-by-inhibition-of-12-15-lipoxygenase-prevents-ros-mediated-cell-death-after-hepatic-ischemia-and-reperfusion
#11
Moritz Drefs, Michael N Thomas, Markus Guba, Martin K Angele, Jens Werner, Marcus Conrad, Christian J Steib, Lesca M Holdt, Joachim Andrassy, Andrej Khandoga, Markus Rentsch
BACKGROUND: Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. METHODS: Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28809482/structural-dynamics-of-15-lipoxygenase-2-via-hydrogen-deuterium-exchange
#12
Kristin Diane Droege, Mary E Keithly, Charles R Sanders, Richard N Armstrong, Matthew K Thompson
Eicosanoids are inflammatory signaling lipids that are biosynthesized in response to cellular injury or threat. They were originally thought to be pro-inflammatory molecules, but at least one sub-class, the lipoxins, are able to resolve inflammation. The first step in lipoxin synthesis is the oxygenation of arachidonic acid by 15-Lipoxygenase (15-LOX). 15-LOX contains two domains: a Ca2+ binding PLAT domain and a catalytic domain. 15-LOX is a soluble cytosolic protein until Ca2+ binding to the PLAT domain promotes translocation to the membrane surface...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28806719/comparison-of-reactive-oxygen-species-metabolism-during-grape-berry-development-between-kyoho-and-its-early-ripening-bud-mutant-fengzao
#13
Fei-Fei Xi, Li-Li Guo, Yi-He Yu, Yan Wang, Qiong Li, Hui-Li Zhao, Guo-Hai Zhang, Da-Long Guo
Enzymes and non-enzyme elements related to the metabolism of reactive oxygen species (ROS), such as catalase (CAT), superoxide dismutase (SOD), ascorbic acid (AsA), glutathione (GSH), NADPH oxidase (NOX), hydrogen peroxide (H2O2), superoxide anion (O2(-)), lipoxygenase (LOX) and malondialdehyde (MDA), were measured in 'Kyoho' and its early ripening bud mutant 'Fengzao' to compare ROS level changes and investigate the potential roles of ROS in grape berry development and the ripening process. In addition, the anthocyanin and sugar contents as well as berry diameter were also investigated at different berry development stages...
August 9, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28780158/corrigendum-to-easy-and-rapid-preparation-of-benzoylhydrazides-and-their-diazene-derivatives-as-inhibitors-of-15-lipoxygenase-bioorg-med-chem-lett-27-2017-1649-1653
#14
Cristian Tirapegui, Williams Acevedo-Fuentes, Pablo Dahech, Claudia Torrent, Pablo Barrias, Macarena Rojas-Poblete, Carolina Mascayano
No abstract text is available yet for this article.
August 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28770377/1-6-o-o-diacetylbritannilactone-inhibits-eotaxin-1-and-alox15-expression-through-inactivation-of-stat6-in-a549-cells
#15
Xi Chen, Ning Ji, Nan Qin, Sheng-An Tang, Ran Wang, Yuling Qiu, Hongquan Duan, Dexin Kong, Meihua Jin
1,6-O,O-Diacetylbritannilactone (OODBL), a plant sesquiterpene lactone, was previously reported to show multiple pharmacological effects such as anti-cancer and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effect of OODBL on interleukin (IL)-4-induced signal transducer and activator of transcription 6 (STAT6) signaling pathway in human lung A549 cells. We found that OODBL dramatically inhibited IL-4-induced messenger RNA (mRNA) expression of eotaxin-1 and arachidonate 15-lipoxygenase-1 (ALOX15) in a dose-dependent manner...
August 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28764037/antioxidant-action-of-fermented-grain-food-supplement-scavenging-of-peroxyl-radicals-and-inhibition-of-plasma-lipid-oxidation-induced-by-multiple-oxidants
#16
Mayuko Morita, Yuji Naito, Etsuo Niki, Toshikazu Yoshikawa
Unregulated oxidative modification of biological molecules induced by multiple oxidants in vivo has been implicated in the pathogenesis of various diseases. Accordingly, the role of antioxidants contained in foods in the maintenance of health and prevention of diseases has received much attention. The efficacy of antioxidants against oxidative stress depends on the nature of oxidants. In the present study, the antioxidant action of fermented grain food supplement, Antioxidant Biofactor (AOB), for scavenging peroxyl radical and inhibition of plasma lipid oxidation induced by multiple oxidants was measured...
December 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28763983/biogenic-antioxidative-and-anti-inflammatory-aryl-polyketides-from-the-venerid-bivalve-clam-paphia-malabarica
#17
Minju Joy, Kajal Chakraborty
Chemical investigation of ethyl acetate-methanol extract of the venerid bivalve clam Paphia malabarica led to isolation of three unprecedented aryl polyketide derivatives, characterized as (E)-12-(17-ethyl-tetrahydro-16-hydroxy-15-(methyl pentanoate)-14-oxo-2H-pyran-13-yl)-9-methyl-but-11-enyl benzoate (1), isobutyl-13-(6-(benzoyloxy)-10-methylpentyl)-tetrahydro-13-methyl-2H-pyran-17-carboxylate (2) and (13-(methoxycarbonyl)-11-((E)-18-ethylhexa-16,19-dienyl)-12-propyl-cyclohex-10-enyl)-methyl-3-hydroxy benzoate (3)...
December 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28763131/the-effect-of-allergen-induced-bronchoconstriction-on-concentration-of-5-oxo-ete-in-exhaled-breath-condensate-of-house-dust-mite-allergic-patients
#18
Krzysztof Kowal, Anna Gielicz, Marek Sanak
BACKGROUND: Arachidonic acid metabolites regulate several aspects of airway function including inflammation, muscle contraction and mucous secretion. OBJECTIVE: The aim of this study was to evaluate concentration of selected 5-lipoxygenase (LOX) and cyclooxygenase (COX)-derived eicosanoids in exhaled breath condensate (EBC) during allergen induced bronchoconstriction. METHODS: The study was performed on 24 allergic rhinitis/asthma patients sensitized to a house dust mite (HDM) Dermatophagoides pteronyssinus (Dp) and 13 healthy controls (HCs)...
August 1, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28757355/15-lipoxygenase-1-re-expression-in-colorectal-cancer-alters-endothelial-cell-features-through-enhanced-expression-of-tsp-1-and-icam-1
#19
Sinem Tunçer, Ayşe Gökçe Keşküş, Melis Çolakoğlu, Ismail Çimen, Caner Yener, Özlen Konu, Sreeparna Banerjee
15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28724635/heterodimers-of-the-transcriptional-factors-nfatc3-and-fosb-mediate-tissue-factor-expression-for-15-s-hydroxyeicosatetraenoic-acid-induced-monocyte-trafficking
#20
Sivareddy Kotla, Nikhlesh K Singh, Daniel Kirchhofer, Gadiparthi N Rao
Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1...
September 8, 2017: Journal of Biological Chemistry
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