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15 lipoxygenase

Jessica L H Walters, Geoffry N De Iuliis, Matthew D Dun, Robert John Aitken, Eileen A McLaughlin, Brett Nixon, Elizabeth G Bromfield
One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15)...
March 13, 2018: Biology of Reproduction
Delphine Lumbroso, Soaad Soboh, Avi Maimon, Sagie Schif-Zuck, Amiram Ariel, Tal Burstyn-Cohen
The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood...
2018: Frontiers in Immunology
Vasundhara Kain, Kevin A Ingle, Janusz Kabarowski, Stephen Barnes, Nita A Limdi, Sumanth D Prabhu, Ganesh V Halade
12/15 lipoxygenase (LOX) directs inflammation and lipid remodeling. However, the role of 12/15LOX in post-myocardial infarction (MI) left ventricular remodeling is unclear. To determine the role of 12/15LOX, 8-12 week-old C57BL/6 J wild-type (WT; n = 93) and 12/15LOX-/- (n = 97) mice were subjected to permanent coronary artery ligation and monitored at day (d)1 and d5 post-operatively. Post-MI d28 survival was measured in male and female mice. No-MI surgery mice were maintained as d0 naïve controls...
March 8, 2018: Journal of Molecular and Cellular Cardiology
Bagora Bayala, Imaël H N Bassole, Salwan Maqdasy, Silvère Baron, Jacques Simpore, Jean-Marc A Lobaccaro
Cymbopogon species are used as traditional remedies in Burkina Faso for treating several diseases. We aimed to study the effects of their essential oils on cancer cell lines. For that purpose, Cymbopogon citratus (DC.) Stapf. and Cymbopogon giganteus Chiov. were studied for their essential oils after various chemical extractions. Antioxidant, potential anti-inflammatory action (inhibition of lipoxygenase) and cytotoxic activities were also tested on various prostate cancer and glioblastoma cell lines. Thirty-three compounds were identified in the essential oil of C...
February 28, 2018: Biochimie
Nannan Wang, Xiaoning Zhao, Jiaxin Huai, Yiran Li, Congcong Cheng, Kaishun Bi, Ronghua Dai
ETHNOPHARMACOLOGICAL RELEVANCE: Huo Luo Xiao Ling Dan (HLXLD), a traditional Chinese medicine (TCM), is commonly used for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: To explore the potential therapeutic mechanism of HLXLD on anti-inflammatory activity. MATERIALS AND METHODS: A metabolomic approach based on UFLC-MS/MS to profile arachidonic acid (AA) metabolic changes was used. The cyclooxygenase (COX) and lipoxygenase (LOX) catalyzed metabolites in plasma were quantified on 7, 14, 21, and 28 days after the rats injected with Complete Freund's adjuvant and orally administrated with HLXLD, methotrexate and dexamethasone in parallel as the positive control drugs...
February 20, 2018: Journal of Ethnopharmacology
Tamas Kriska, Michael J Thomas, John R Falck, William B Campbell
Polarization of macrophages to pro-inflammatory M1 and to anti-inflammatory alternatively activated M2 states has physiological implications in development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acids (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction...
February 22, 2018: Journal of Lipid Research
Khaled Elmasry, Ahmed S Ibrahim, Heba Saleh, Nehal Elsherbiny, Sally Elshafey, Khaled A Hussein, Mohamed Al-Shabrawey
AIMS/HYPOTHESIS: Our earlier studies have established the role of 12/15-lipoxygenase (LO) in mediating the inflammatory reaction in diabetic retinopathy. However, the exact mechanism is still unclear. The goal of the current study was to identify the potential role of endoplasmic reticulum (ER) stress as a major cellular stress response in the 12/15-LO-induced retinal changes in diabetic retinopathy. METHODS: We used in vivo and in vitro approaches. For in vivo studies, experimental diabetes was induced in wild-type (WT) mice and 12/15-Lo (also known as Alox15) knockout mice (12/15-Lo-/- ); ER stress was then evaluated after 12-14 weeks of diabetes...
February 21, 2018: Diabetologia
Yosuke Isobe, Yusuke Kawashima, Tomoaki Ishihara, Kenji Watanabe, Osamu Ohara, Makoto Arita
The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of greatest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE...
February 20, 2018: ACS Chemical Biology
Haruto Yamanashi, William E Boeglin, Christophe Morisseau, Robert W Davis, Gary A Sulikowski, Bruce D Hammock, Alan R Brash
Lipoxygenase-catalyzed oxidation of the essential fatty acid linoleate represents a vital step in construction of the mammalian epidermal permeability barrier. Analysis of epidermal lipids indicates the linoleate is converted to a trihydroxy derivative by hydrolysis of an epoxy-hydroxy precursor. We evaluated different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and compared the products to those of acid-catalyzed hydrolysis. In the absence of enzyme, exposure to pH 5 or pH 6 at 37 deg C for 30 min hydrolyzed fatty acid allylic epoxyalcohols to four trihydroxy products...
February 19, 2018: Journal of Lipid Research
Delphine L Chen, Howard J Huang, Derek E Byers, Adrian Shifren, Bryan Belikoff, Jacquelyn T Engle, Elizabeth Arentson, Debra Kemp, Sharon Phillips, David E Scherrer, Hideji Fujiwara, Katherine J Spayd, Frank J Brooks, Richard A Pierce, Mario Castro, Warren Isakow
BACKGROUND: Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation...
2018: PloS One
Seyed Jamal Alavi, Hamid Sadeghian, Seyed Mohammad Seyedi, Alireza Salimi, Hossein Eshghi
Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipoxygenase enzymes. Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin (7-M3HC) derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result...
February 1, 2018: Chemical Biology & Drug Design
Xiaoqun Wang, Chang Li, Jie Gao, Zhuhui Liu, Jiawei Chen, Ruiyan Zhang, Weifeng Shen, Lin Lu
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Haydi Saher ElBordiny, Mostafa Mahmoud El-Miligy, Shaymaa Emam Kassab, Hoda Daabees, Soad Abdelhamid Mohamed El-Hawash, Waleed Ali Mohamed Ali
New candidates of 3-(4,5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives (4-7) were designed combining the pyrazoline/isoxazoline heterocycles and 2-phenylindole to explore its potential as 15-lipoxygenase (15-LOX) inhibitors. The design of the new derivatives was based on utilizing the antioxidant properties of pyrazoline, 2-phenylindole and the good 15-LOX inhibition properties of indolylpyrazoline. The derivatives were synthesized adopting simple and laboratory friendly reaction conditions to give the target compounds in quantitative yields...
January 10, 2018: European Journal of Medicinal Chemistry
Oliver Werz, Jana Gerstmeier, Stephania Libreros, Xavier De la Rosa, Markus Werner, Paul C Norris, Nan Chiang, Charles N Serhan
Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1...
January 4, 2018: Nature Communications
Liudmila L Mazaleuskaya, Ashkan Salamatipour, Dimitra Sarantopoulou, Liwei Weng, Garret A FitzGerald, Ian A Blair, Clementina Mesaros
The biosynthesis of eicosanoids occurs enzymatically via lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P450, or through non-enzymatic free radical reactions. The enzymatic routes are highly enantiospecific. Chiral separation and high sensitivity detection methods are required to differentiate and quantify enantioselective HETEs (hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acids) in complex biological fluids. We report here a targeted chiral lipidomics analysis of human blood using ultrahigh performance liquid chromatgraphy (UHPLC)-electron capture atmospheric pressure chemical ionization/high resolution mass spectrometry (ECAPCI/HRMS)...
January 4, 2018: Journal of Lipid Research
Adriana Trifan, Sebastian E W Opitz, Roland Josuran, Andreas Grubelnik, Nils Esslinger, Samuel Peter, Sarah Bräm, Nadja Meier, Evelyn Wolfram
Comfrey root preparations are used for the external treatment of joint distortions and myalgia, due to its analgesic and anti-inflammatory properties. Up to date, key activity-determining constituents of comfrey root extracts have not been completely elucidated. Therefore, we applied different approaches to further characterize a comfrey root extract (65% ethanol). The phenolic profile of comfrey root sample was characterized by HPLC-DAD-QTOF-MS/MS. Rosmarinic acid was identified as main phenolic constituent (7...
December 27, 2017: Food and Chemical Toxicology
Andreas Douros, Dimitra Hadjipavlou-Litina, Konstantinos Nikolaou, Helen Skaltsa
The phytochemical analysis of the polar extracts of Cedrus brevifolia needles yielded 20 compounds, namely from the methanol extract we isolated three flavonoids (1-3), one hydrolysable tannin (4), eleven phenolic derivatives (5-15) and one apocarotenoid (16), while from the methanol: water (5:1) extract we isolated four flavonoids (17-20). Chemical structures of all isolated compounds were determined by 1D, 2D-NMR (1 Dimension, 2 Dimensions Nuclear Magnetic Resonance) and UV-Vis (Ultraviolet-Visible) spectroscopy...
December 27, 2017: Plants (Basel, Switzerland)
Fatemeh Mohammadipanah, Mana Momenilandi
CONTEXT: Actinobacteria are a precious source of novel bioactive metabolites with potential pharmaceutical applications. OBJECTIVES: Representatives of 11 genera of rare Actinobacteria were selected for the evaluation of antioxidant activity. MATERIAL AND METHODS: Fermentation broths of the Actinobacteria were extracted and dosage of 10 to 2000 µg/mL were applied for in vitro antioxidant-related bioassays. Cytotoxicity was assessed at the concentration of 2...
December 2018: Pharmaceutical Biology
Christabel Fung-Yih Ho, Claire Poh-Ee Bon, Yee-Kong Ng, Deron R Herr, Jui-Sheng Wu, Teng-Nan Lin, Wei-Yi Ong
The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA) is enriched in neural membranes of the CNS, and recent studies have shown a role of DHA metabolism by 15-lipoxygenase-1 (Alox15) in prefrontal cortex resolvin D1 formation, hippocampo-prefrontal cortical long-term-potentiation, spatial working memory, and anti-nociception/anxiety. In this study, we elucidated epigenetic regulation of Alox15 via histone modifications in neuron-like cells. Treatment of undifferentiated SH-SY5Y human neuroblastoma cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate significantly increased Alox15 mRNA expression...
December 12, 2017: Neurochemical Research
Liang Zong, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiguang Ma, Cancan Zhou, Qinhong Xu, Wanxing Duan, Liang Han, Jianjun Lei, Xuqi Li, Qingyong Ma, Zheng Wang
BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated. METHODS: Pancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays...
December 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
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