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https://www.readbyqxmd.com/read/29097313/isomer-distribution-of-hydroxyoctadecadienoates-hode-and-hydroxyeicosatetraenoates-hete-produced-in-the-plasma-oxidation-mediated-by-peroxyl-radical-peroxynitrite-hypochlorite-15-lipoxygenase-and-singlet-oxygen
#1
Aya Umeno, Mayuko Morita, Yasukazu Yoshida, Yuji Naito, Etsuo Niki
Free and ester forms of unsaturated fatty acids and cholesterol are oxidized in vivo by multiple oxidants to give diverse products. Some lipid oxidation is mediated by enzymes to selectively give specific products, while others proceed randomly to produce mixtures of many kinds of regioisomers and stereoisomers. The efficacy of antioxidants against lipid oxidation depends on the nature of the oxidants and therefore the identification of oxidant is important for understanding the roles and effects of lipid oxidation and antioxidants in vivo...
October 31, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29095817/a-regulatory-role-for-%C3%AE-adrenergic-receptors-regarding-the-resolvin-d1-rvd1-pathway-in-the-diabetic-retina
#2
Haoshen Shi, Thomas W Carion, Youde Jiang, Adam Chahine, Jena J Steinle, Elizabeth A Berger
Diabetic retinopathy is a visually debilitating disease with limited treatment options available. Compound 49b, a β-adrenergic receptor agonist, has been demonstrated to effectively reduce disease pathogenesis associated with diabetic retinopathy. While the exact mechanisms are not fully understood, previous studies have determined that it reduces the pro-inflammatory cytokine, TNF-α, and inhibits apoptosis of the retinal microvasculture. As inflammation becomes more recognized in driving disease pathogenesis, so does the regulation by pro-resolving pathways as therapeutic points of intervention...
2017: PloS One
https://www.readbyqxmd.com/read/29079502/inhibiting-12-15-lipoxygenase-to-treat-acute-stroke-in-permanent-and-tpa-induced-thrombolysis-models
#3
H Karatas, Joo Eun Jung, E H Lo, K van Leyen
12/15-Lipoxygenase (12/15-LOX) contributes to the brain damage after middle cerebral artery occlusion (MCAO) in the acute phase of stroke. The aim of this study was to investigate the effects of a 12/15-LOX inhibitor, LOXBlock-1(LB1), in mice using a FeCl3-induced permanent distal MCAO model and FeCl3-induced ischemia/thrombolysis with tPA. In order to induce permanent distal MCAO, 30% FeCl3 was used in C57BL6 mice. LB1 or DMSO treatments were applied intraperitoneally 2hrs following MCAO. For FeCl3-induced ischemia/thrombolysis experiments, 10% FeCl3 was preferred so as to obtain reperfusion with tPA in CD1 mice...
October 24, 2017: Brain Research
https://www.readbyqxmd.com/read/29068244/interaction-between-alox15-polymorphisms-and-coronary-artery-disease-in-north-indian-population
#4
Naindeep Kaur, Jagtar Singh, Sreenivas Reddy
BACKGROUND: Coronary artery disease (CAD) is major cause of death and morbidity worldwide. Arachidonate 12/15-lipoxygenase (ALOX) is a member of the lipid peroxidizing enzyme family and implicated in the pathogenesis of atherosclerosis, but with contradicting results. AIM: The present study aimed to investigate the association of two polymorphisms in ALOX15 (rs2619112 and rs7217186) and the risk of CAD in North Indian population. METHODS: A total of 500 angiographically confirmed CAD patients and 500 control subjects of North Indian population were recruited in the case-control study and genotyped by PCR-RFLP...
October 25, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29064442/enhanced-glucose-uptake-in-human-liver-cells-and-inhibition-of-carbohydrate-hydrolyzing-enzymes-by-nordic-berry-extracts
#5
Giang Thanh Thi Ho, Thi Kim Yen Nguyen, Eili Tranheim Kase, Margey Tadesse, Hilde Barsett, Helle Wangensteen
A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE)...
October 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29053969/pebp1-wardens-ferroptosis-by-enabling-lipoxygenase-generation-of-lipid-death-signals
#6
Sally E Wenzel, Yulia Y Tyurina, Jinming Zhao, Claudette M St Croix, Haider H Dar, Gaowei Mao, Vladimir A Tyurin, Tamil S Anthonymuthu, Alexandr A Kapralov, Andrew A Amoscato, Karolina Mikulska-Ruminska, Indira H Shrivastava, Elizabeth M Kenny, Qin Yang, Joel C Rosenbaum, Louis J Sparvero, David R Emlet, Xiaoyan Wen, Yoshinori Minami, Feng Qu, Simon C Watkins, Theodore R Holman, Andrew P VanDemark, John A Kellum, Ivet Bahar, Hülya Bayır, Valerian E Kagan
Ferroptosis is a form of programmed cell death that is pathogenic to several acute and chronic diseases and executed via oxygenation of polyunsaturated phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO substrate specificity are enigmatic. We sought a common ferroptosis regulator for 15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their substrate competence to generate hydroperoxy-PE...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053142/resolution-of-inflammation-and-sepsis-survival-are-improved-by-dietary-%C3%AE-3-fatty-acids
#7
Andreas Körner, Martin Schlegel, Julia Theurer, Hannes Frohnmeyer, Michael Adolph, Marieke Heijink, Martin Giera, Peter Rosenberger, Valbona Mirakaj
Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration...
October 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29048783/-investigation-on-silymarin-impact-on-lipopolysaccharide-induced-inflammation-model-based-on-arachidonic-acid-metabolism-pathway
#8
Danti Mai, Chan Yang, Yun Xue, Yan Wang, Chao Yan
The objective of this research is to investigate the suppressive effect of silymarin on vitro cell culture model of inflammatory macrophage RAW264.7 induced by Kdo2-Lipid A, and explore its mechanism based on cell metabonomics. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was used in the cell metabonomic assay to quantitative analysis of metabolites related to eicosanoids pathway. Then chemometric approaches such as principal component analysis were used to process the metabolic data...
June 8, 2017: Se Pu, Chinese Journal of Chromatography
https://www.readbyqxmd.com/read/29022900/increased-15-lipoxygenase-1-expression-in-chondrocytes-contributes-to-the-pathogenesis-of-osteoarthritis
#9
Kaizhe Chen, Yufei Yan, Changwei Li, Jun Yuan, Fei Wang, Ping Huang, Niandong Qian, Jin Qi, Hanbing Zhou, Qi Zhou, Lianfu Deng, Chuan He, Lei Guo
15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The purpose of this study was to determine the potential role of 15-LO-1 in osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western blotting and quantitative real-time PCR in articular cartilage from the OA rat models and OA patients. To further investigate the effects of 15-LO-1 on chondrocyte functions, such as extracellular matrix (ECM) secretion, the release of matrix-degrading enzymes, the production of reactive oxygen species (ROS), cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid encoding 15-LO-1, respectively...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28993759/the-four-way-stop-sign-viruses-12-lipoxygenase-islets-and-natural-killer-cells-in-type-1-diabetes-progression
#10
Michele L Semeraro, Lindsey M Glenn, Margaret A Morris
Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28986357/excess-omega-6-fatty-acids-influx-in-aging-drives-metabolic-dysregulation-electrocardiographic-alterations-and-low-grade-chronic-inflammation
#11
Vasundhara Kain, Kevin A Ingle, Maureen Kachman, Heidi Baum, Gobinath Shanmugam, Namakkal S Rajasekaran, Martin E Young, Ganesh V Halade
Maintaining a balance of omega-6 and -3 fatty acids is essential for cardiac health. Current omega-6 and omega-3 fatty acids in the American diet has shifted from the ideal ratio of 2:1 to almost 20:1, while there is a body of evidence suggest the negative impact of such a shift in younger organisms, the underlying age-related metabolic signaling in response to the excess influx of omega-6 is incompletely understood. In the current study, young (6-month-old) and aging (≥18-month-old) mice were fed for two months with omega-6 enriched diet...
October 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28986132/new-perspectives-in-cancer-modulation-of-lipid-metabolism-and-inflammation-resolution
#12
REVIEW
Nella Prevete, Federica Liotti, Angela Amoresano, Piero Pucci, Amato de Paulis, Rosa Marina Melillo
Inflammation is considered an enabling feature of cancer. Besides the persistence of inflammatory stimuli, also defective mechanisms of resolution can lead to chronic inflammation. Inflammation resolution is an active process controlled by lipidic specialized pro-resolving mediators (SPMs), derived from ω-3 or ω-6 essential polyunsaturated fatty acids (PUFA) through the activity of lipoxygenases (ALOX5 and 15). Thus, a lack or defect in resolution mechanisms may affect cancer development and progression by prolonging inflammation...
October 3, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28981785/methyl-jasmonate-induced-emission-of-biogenic-volatiles-is-biphasic-in-cucumber-a-high-resolution-analysis-of-dose-dependence
#13
Yifan Jiang, Jiayan Ye, Shuai Li, Ülo Niinemets, Peter Bozhkov
Methyl jasmonate (MeJA) is a key airborne elicitor activating jasmonate-dependent signaling pathways, including induction of stress-related volatile emissions, but how the magnitude and timing of these emissions scale with MeJA dose is not known. Treatments with exogenous MeJA concentrations ranging from mild (0.2 mM) to lethal (50 mM) were used to investigate quantitative relationships among MeJA dose and the kinetics and magnitude of volatile release in Cucumis sativus by combining high-resolution measurements with a proton-transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) and GC-MS...
July 20, 2017: Journal of Experimental Botany
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
#14
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
#15
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
#16
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/TOF-MS was applied to collect MS/MS spectra for the OxPLs...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28854238/elastic-network-model-of-learned-maintained-contacts-to-predict-protein-motion
#17
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
#18
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
#19
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...
October 20, 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
#20
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 proinflammatory 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...
November 2017: Diabetes
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