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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
#1
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...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28723225/preferential-generation-of-15-hete-pe-induced-by-il-13-regulates-goblet-cell-differentiation-in-human-airway-epithelial-cells
#2
Jinming Zhao, Yoshinori Minami, Emily Etling, John M Coleman, Sarah N Lauder, Victoria Tyrrell, Maceler Aldrovandi, Valerie O'Donnell, Hans-Erik Claesson, Valerian Kagan, Sally Wenzel
RATIONALE: Type-2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase (15LO1) is induced by the Type-2 cytokines/IL-13 in human airway epithelial cells (HAEC) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15-HETE-phosphatidyethanoloamine (PE) (15-HETE-PE) and 13-hydroxyoctadecadienoic acid (13-HODE). The current study investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, and the influence on goblet cell differentiation in HAECs...
July 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28721338/is-aortic-aneurysm-preventable
#3
Undurti N Das
Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)...
June 2017: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28720379/inhibition-of-12-15-lox-ameliorates-cognitive-and-cholinergic-dysfunction-in-mouse-model-of-hypobaric-hypoxia-via-attenuation-of-oxidative-nitrosative-stress
#4
Richa Choudhary, Udayabanu Malairaman, Anju Katyal
12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia-induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX...
July 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28704416/genetic-variation-in-the-eicosanoid-pathway-is-associated-with-non-small-cell-lung-cancer-nsclc-survival
#5
Lindsay N Sausville, Carissa C Jones, Melinda C Aldrich, William J Blot, Ambra Pozzi, Scott M Williams
Globally, lung cancer results in more deaths worldwide than any other cancer, indicating a need for better treatments. Members of the eicosanoid metabolism pathway represent promising therapeutic targets, as several enzymes involved in the generation of these lipids are dysregulated in many cancers and their inhibition reduces lung cancer growth in mouse models. However, genetic variation of enzymes involved in eicosanoid metabolism has not been adequately examined for association with lung cancer. The goal of this study was to determine whether germline genetic variation altering eicosanoid producing enzyme function and/or expression are associated with differences in lung cancer survival...
2017: PloS One
https://www.readbyqxmd.com/read/28701173/15-oxoeicosatetraenoic-acid-mediates-monocyte-adhesion-to-endothelial-cell
#6
Guohua Ma, Bing Pan, Sufen Ren, Caixia Guo, Yansong Guo, Lixin Wei, Lemin Zheng, Buxing Chen
BACKGROUND: A great number of studies reported that 12/15-lipoxygenase (12/15-LO) played an important role in atherosclerosis. And its arachidonic acid(AA) metabolite, 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15(S)-HETE), is demonstrated to mediate endothelial dysfunction. 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE. However, relatively little is known about the biological effects of 15-oxo-ETE in cardiovascular disease...
July 12, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28694081/deletion-of-12-15-lipoxygenase-accelerates-the-development-of-aging-associated-and-instability-induced-osteoarthritis
#7
L Habouri, F E El Mansouri, Y Ouhaddi, B Lussier, J-P Pelletier, J Martel-Pelletier, M Benderdour, H Fahmi
OBJECTIVE: 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA. METHODS: The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) mice...
July 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28691068/hydrogen-deuterium-exchange-of-lipoxygenase-uncovers-a-relationship-between-distal-solvent-exposed-protein-motions-and-the-thermal-activation-barrier-for-catalytic-proton-coupled-electron-tunneling
#8
Adam R Offenbacher, Shenshen Hu, Erin M Poss, Cody A M Carr, Alexander D Scouras, Daniil M Prigozhin, Anthony T Iavarone, Ali Palla, Tom Alber, James S Fraser, Judith P Klinman
Defining specific pathways for efficient heat transfer from protein-solvent interfaces to their active sites represents one of the compelling and timely challenges in our quest for a physical description of the origins of enzyme catalysis. Enzymatic hydrogen tunneling reactions constitute excellent systems in which to validate experimental approaches to this important question, given the inherent temperature independence of quantum mechanical wave function overlap. Herein, we present the application of hydrogen-deuterium exchange coupled to mass spectrometry toward the spatial resolution of protein motions that can be related to an enzyme's catalytic parameters...
June 28, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28690055/antitumor-effect-of-ferula-assa-foetida-oleo-gum-resin-against-breast-cancer-induced-by-4t1-cells-in-balb-c-mice
#9
Seyyed Majid Bagheri, Amir Abdian-Asl, Mahin Taheri Moghadam, Maryam Yadegari, Aghdas Mirjalili, Fatemeh Zare-Mohazabieh, Haniyeh Momeni
BACKGROUND: Ferula assa foetida commonly consumed as a healthy beverage has been demonstrated to have various biological activities, including antioxidation, anti-obesity and anti-cancer. OBJECTIVE: Our study aims to investigate the antitumor effect of asafoetida in vivo using mouse mammary carcinoma 4T1 cells. MATERIALS AND METHODS: In the study, female BALB/c mice were divided into two groups (n = 6), which were control (untreated) and other group of mice with breast cancer treated with 100 mg/kg of asafoetida, respectively, by oral gavage...
July 6, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28668243/effect-of-misoprostol-on-patients-with-aspirin-exacerbated-respiratory-disease-undergoing-aspirin-challenge-and-desensitization
#10
Kristen M Walters, Ronald A Simon, Katharine M Woessner, Nathan E Wineinger, Andrew A White
BACKGROUND: Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. OBJECTIVE: To examine whether misoprostol (oral prostaglandin E1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD...
July 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28611577/the-anti-inflammatory-effects-of-lipoxygenase-and-cyclo-oxygenase-inhibitors-in-inflammation-induced-human-fetal-glia-cells-and-the-a%C3%AE-degradation-capacity-of-human-fetal-astrocytes-in-an-ex-vivo-assay
#11
Rea Pihlaja, Merja Haaparanta-Solin, Juha O Rinne
Chronic inflammation is a common phenomenon present in the background of multiple neurodegenerative diseases, including Alzheimer's disease (AD). The arachidonic acid pathway overproduces proinflammatory eicosanoids during these states and glial cells in the brain gradually lose their vital functions of protecting and supporting neurons. In this study, the role of different key enzymes of the eicosanoid pathway mediating inflammatory responses was examined in vitro and ex vivo using human fetal glial cells...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28595877/lipoxygenase-inhibitors-protect-acute-lymphoblastic-leukemia-cells-from-ferroptotic-cell-death
#12
Lukas Probst, Jasmin Dächert, Barbara Schenk, Simone Fulda
Ferroptosis has recently been identified as a mode of programmed cell death. However, little is yet known about the signaling mechanisms. Here, we report that lipoxygenases (LOX) contribute to the regulation of RSL3-induced ferroptosis in acute lymphoblastic leukemia (ALL) cells. We show that the glutathione (GSH) peroxidase 4 (GPX4) inhibitor RSL3 triggers lipid peroxidation, production of reactive oxygen species (ROS) and cell death in ALL cells. All these events are impeded in the presence of Ferrostatin-1 (Fer-1), a small-molecule inhibitor of lipid peroxidation...
June 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28579398/evaluation-of-the-expression-level-of-12-15-lipoxygenase-and-the-related-inflammatory-factors-ccl5-ccl3-in-respiratory-syncytial-virus-infection-in-mice-model
#13
Vahid Salimi, Ali Ramezani, Habibollah Mirzaei, Alireza Tahamtan, Ebrahim Faghihloo, Farhad Rezaei, Maryam Naseri, Louis Bont, Talat Mokhtari-Azad, Masoumeh Tavakoli-Yaraki
Human respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. Disease is thought to be caused, at least partially, by an excessive immune response. Pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. Lipoxygenases (LOXs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate inflammation and have been suggested to play an important role in the immune response in viral infection...
June 1, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28566527/interactions-between-5-lipoxygenase-polymorphisms-and-adipose-tissue-contents-of-arachidonic-and-eicosapentaenoic-acids-do-not-affect-risk-of-myocardial-infarction-in-middle-aged-men-and-women-in-a-danish-case-cohort-study
#14
Anders Gammelmark, Søren Lundbye-Christensen, Anne Tjønneland, Erik B Schmidt, Kim Overvad, Michael S Nielsen
Background: The 5-lipoxygenase pathway has been linked to atherothrombotic disease, and a functional tandem repeat polymorphism in the arachidonate lipoxygenase-5 (ALOX-5) gene has been associated with the risk of myocardial infarction (MI). Interestingly, 2 studies have reported an interaction between dietary intakes of the ALOX-5 substrates, arachidonic acid (AA) and eicosapentaenoic acid (EPA), and genotype.Objective: We investigated whether the interactions between the ALOX-5 tandem repeat polymorphism (rs59439148) and adipose tissue AA and EPA were associated with incident MI...
May 31, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28566277/enzymatic-lipid-oxidation-by-eosinophils-propagates-coagulation-hemostasis-and-thrombotic-disease
#15
Stefan Uderhardt, Jochen A Ackermann, Tobias Fillep, Victoria J Hammond, Johann Willeit, Peter Santer, Manuel Mayr, Markus Biburger, Meike Miller, Katie R Zellner, Konstantin Stark, Alexander Zarbock, Jan Rossaint, Irene Schubert, Dirk Mielenz, Barbara Dietel, Dorette Raaz-Schrauder, Cihan Ay, Thomas Gremmel, Johannes Thaler, Christian Heim, Martin Herrmann, Peter W Collins, Gernot Schabbauer, Nigel Mackman, David Voehringer, Jerry L Nadler, James J Lee, Steffen Massberg, Manfred Rauh, Stefan Kiechl, Georg Schett, Valerie B O'Donnell, Gerhard Krönke
Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28507800/formyl-peptide-receptor-1-suppresses-gastric-cancer-angiogenesis-and-growth-by-exploiting-inflammation-resolution-pathways
#16
Nella Prevete, Federica Liotti, Anna Illiano, Angela Amoresano, Piero Pucci, Amato de Paulis, Rosa Marina Melillo
Chronic inflammation can result from inadequate engagement of resolution mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs) arising from the metabolic activity of lipoxygenases (ALOX5/15) on ω-6 or ω-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by inhibiting its inflammatory/angiogenic potential. In this study, we asked whether FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and growth...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506553/inhibition-of-12-15-lo-ameliorates-cvb3-induced-myocarditis-by-activating-nrf2
#17
Feng Ai, Jiayong Zheng, Yanwei Zhang, Taibing Fan
Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated and involved in the development of heart failure. Nuclear factor E2-related factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and its underlying molecular mechanism have not yet been elucidated. Here, we demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28504669/nitric-oxide-prevents-a-pathogen-permissive-granulocytic-inflammation-during-tuberculosis
#18
Bibhuti B Mishra, Rustin R Lovewell, Andrew J Olive, Guoliang Zhang, Wenfei Wang, Eliseo Eugenin, Clare M Smith, Jia Yao Phuah, Jarukit E Long, Michelle L Dubuke, Samantha G Palace, Jon D Goguen, Richard E Baker, Subhalaxmi Nambi, Rabinarayan Mishra, Matthew G Booty, Christina E Baer, Scott A Shaffer, Veronique Dartois, Beth A McCormick, Xinchun Chen, Christopher M Sassetti
Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. Using M. tuberculosis mutants as indicators of the pathogen's environment, we inferred that granulocytic inflammation generates a nutrient-replete niche that supports M...
May 15, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28502039/possible-involvement-of-the-lipoxygenase-and-leukotriene-signaling-pathways-in-cisplatin-mediated-renal-toxicity
#19
Osama A Alkhamees, Abdulaziz S Alroujayee, Hatem M Abuohashish, Fatima S Alrojayee, Mohammed M Ahmed
PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively...
July 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28496472/synthesis-and-biological-evaluation-of-n-5-pyridin-2-yl-1-3-4-thiadiazol-2-yl-benzamide-derivatives-as-lipoxygenase-inhibitor-with-potential-anticancer-activity
#20
Alireza Aliabadi, Ahmad Mohammadi-Farani, Sahar Roodabeh, Farahnaz Ahmadi
In the recent years, the role of LOX enzymes in the origin of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and the cytotoxicity of the members of this series was assessed using MTT protocol. Enzyme inhibitory activity of the prepared compounds was also tested against 15-lipoxygenase-1 as a novel target for the discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared with doxorubicin...
2017: Iranian Journal of Pharmaceutical Research: IJPR
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