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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
#1
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
#2
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
#3
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
#4
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
#5
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...
May 31, 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
#6
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
#7
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
#8
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
#9
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...
May 13, 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
#10
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
https://www.readbyqxmd.com/read/28492741/effect-of-alox-15-polymorphism-on-gcf-levels-of-lipoxin-a4-in-chronic-periodontitis-a-preliminary-study
#11
Fouzia Tarannum, Mohamed Faizuddin
Lipoxins play an important role in periodontal resolution, hence, investigation of genetic polymorphism of lipoxin gene may provide important information on the role of lipoxins in periodontal disease pathogenesis. The aim of this study was to investigate a polymorphism of C-to-T substitution at position c.-292 in ALOX15 (reticulocyte-type 15 lipoxygenase 1) gene in patients with chronic periodontitis and to associate the polymorphism with gingival crevicular fluid (GCF) lipoxin A4 (LXA4) levels. Forty-five chronic periodontitis and 45 periodontally healthy patients were included in this case-control study...
March 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/28477412/salvia-officinalis-l-essential-oil-from-spain-determination-of-composition-antioxidant-capacity-antienzymatic-and-antimicrobial-bioactivities
#12
Ana-Belen Cutillas, Alejandro Carrasco, Ramiro Martinez-Gutierrez, Virginia Tomas, José Tudela
Four essential oils (EOs) from Salvia officinalis L. cultivated in Spain (Murcia province) were analyzed by gas chromatography coupled with mass spectrometry (GC/MS) to determine their relative and absolute composition. The main components were α-thujone (22.8-41.7%), camphor (10.7-19.8%), 1,8-cineole (4.7-15.6%) and β-thujone (6.1-15.6%). Enantioselective gas chromatography identified (-)-α-thujone and (+)-camphor as the main enantiomers in all the analyzed EOs. Furthermore, when the EOs were tested to determine their antioxidant activity against free radicals and as ferric reducing and ferrous chelating agents, all were seen to have moderate activity due to the compounds they contained, such as linalool or terpinene...
May 6, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28465374/regulation-of-delta-opioid-receptor-mediated-signaling-and-antinociception-in-peripheral-sensory-neurons-by-arachidonic-acid-dependent-12-15-lipoxygenase-metabolites
#13
Laura C Sullivan, Teresa A Chavera, Xiaoli Gao, Miryam M Pando, Kelly A Berg
The function of delta opioid receptors (DOR) expressed by peripheral pain-sensing neurons (nociceptors) is regulated by both cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid (AA) metabolites (Sullivan et al., 2015). Whereas COX metabolites enhance responsiveness, LOX metabolites elicit a refractory, non-signaling state of the DOR receptor system for antinociceptive signaling. In this study, using high performance liquid chromatography tandem mass spectrometry analyses, we have found that the 12/15-LOX metabolites, 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, were elevated following treatment of adult rat primary sensory neuron cultures with AA...
May 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28460604/the-15-lo-1-15-hete-system-promotes-angiogenesis-by-upregulating-vegf-in-ischemic-brains
#14
Li Chen, Yan-Mei Zhu, Yu-Nong Li, Peng-Yan Li, Di Wang, Yu Liu, You-Yang Qu, Da-Ling Zhu, Yu-Lan Zhu
OBJECTIVES: Angiogenesis promotes neurobehavioral recovery after cerebral ischemic stroke. 15(S)-hydroxyeicosatetraenoic acid (15-HETE) is one of the major metabolites of arachidonic acid by 15-lipoxygenase (15-LO) and stimulates the production of vascular endothelial growth factor (VEGF), thus, inducing autocrine-mediated angiogenesis. The present study aimed to investigate the role of 15-LO/15-HETE system on VEGF expression and angiogenesis in brain ischemia. METHODS: Rat cerebral arterial vascular endothelial cells were used to set up a cell injury model of oxygen-glucose deprivation and reoxygenation (OGD/R), mimicking a condition of brain ischemia...
May 1, 2017: Neurological Research
https://www.readbyqxmd.com/read/28436420/key-role-of-15-lo-15-hete-in-angiogenesis-and-functional-recovery-in-later-stages-of-post-stroke-mice
#15
Di Wang, Yu Liu, Li Chen, Pengyan Li, Youyang Qu, Yanmei Zhu, Yulan Zhu
This study sought to clarify the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests to determine functional recovery after stroke. Double immunofluorescence staining of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC proliferation and migration...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28411230/interaction-of-12-15-lipoxygenase-with-fatty-acids-alters-the-leukocyte-kinetics-leading-to-improved-post-myocardial-infarction-healing
#16
Ganesh V Halade, Vasundhara Kain, Kevin A Ingle, Sumanth D Prabhu
The metabolic transformation of fatty acids to form oxylipids using 12/15lipoxygenase (LOX) can promote either resolving or non-resolving inflammation. However, the mechanism of how 12/15LOX interacts with PUFA (polyunsaturated fatty acids) in post-myocardial infarction (MI) healing is unclear. Here, we reported the role of 12/15LOX in post-MI cardiac remodeling in a PUFA (10% w/w, 22 Kcal) enriched environment. Wild-type (WT; C57BL/6J) and 12/15LOX null (12/15LOX(-/-)) male mice of 8-12-weeks age were fed PUFA-enriched diet for 1 month and subjected to permanent coronary artery ligation...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28409415/%C3%AE-aminobutyric-acid-gaba-confers-chromium-stress-tolerance-in-brassica-juncea-l-by-modulating-the-antioxidant-defense-and-glyoxalase-systems
#17
Jubayer Al Mahmud, Mirza Hasanuzzaman, Kamrun Nahar, Anisur Rahman, Md Shahadat Hossain, Masayuki Fujita
Chromium (Cr) toxicity is hazardous to the seed germination, growth, and development of plants. γ-aminobutyric acid (GABA) is a non-protein amino acid and is involved in stress tolerance in plants. To investigate the effects of GABA in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.) seedlings with Cr (0.15 and 0.3 mM K2CrO4, 5 days) alone and in combination with GABA (125 µM) in a semi-hydroponic medium. The roots and shoots of the seedlings accumulated Cr in a dose-dependent manner, which led to an increase in oxidative damage [lipid peroxidation; hydrogen peroxide (H2O2) content; superoxide (O2(•-)) generation; lipoxygenase (LOX) activity], methylglyoxal (MG) content, and disrupted antioxidant defense and glyoxalase systems...
April 13, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28403941/obesity-is-positively-associated-with-arachidonic-acid-derived-5-and-11-hydroxyeicosatetraenoic-acid-hete
#18
Charles Austin Pickens, Lorraine M Sordillo, Chen Zhang, Jenifer I Fenton
BACKGROUND: Oxylipids are oxygenated polyunsaturated fatty acid (PUFA) metabolites that are responsible for the onset and resolution of the inflammatory response. Enzymatic oxygenation through the lipoxygenase (LOX) or cytochrome P450 (CYP) pathways can form oxylipids that have either proinflammatory or proresolving functions depending on the type of PUFA substrate and degree of metabolism. The objective of this study was to determine how PUFA substrates and their corresponding oxylipids are associated with obesity...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28393703/mir-106a-is-associated-with-diabetic-peripheral-neuropathy-through-the-regulation-of-12-15-lox-mediated-oxidative-nitrative-stress
#19
Yuanbo Wu, Dandan Xu, Xiang Zhu, Guangwei Yang, Mingshan Ren
BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that with a complex pathogenesis. Study has reported that oxidative stress and nitrative stress were all involved in the DPN, however, the mechanism between them was still unclear. In the present study, we investigated whether miR-106a signaling regulated 12/15-Lipoxygenase (12/15-LOX) on oxidative/nitrative stress in DPN. METHODS: Dorsal root ganglion (DRG) was isolated from 10 healthy mice and 10 DPN mice...
April 4, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28386601/on-the-mechanism-of-cytoprotection-by-ferrostatin-1-and-liproxstatin-1-and-the-role-of-lipid-peroxidation-in-ferroptotic-cell-death
#20
Omkar Zilka, Ron Shah, Bo Li, José Pedro Friedmann Angeli, Markus Griesser, Marcus Conrad, Derek A Pratt
Ferroptosis is a form of regulated necrosis associated with the iron-dependent accumulation of lipid hydroperoxides that may play a key role in the pathogenesis of degenerative diseases in which lipid peroxidation has been implicated. High-throughput screening efforts have identified ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent inhibitors of ferroptosis - an activity that has been ascribed to their ability to slow the accumulation of lipid hydroperoxides. Herein we demonstrate that this activity likely derives from their reactivity as radical-trapping antioxidants (RTAs) rather than their potency as inhibitors of lipoxygenases...
March 22, 2017: ACS Central Science
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