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https://www.readbyqxmd.com/read/29780994/molecular-mechanism-of-15-lipoxygenase-allosteric-activation-and-inhibition
#1
Hu Meng, Ziwei Dai, Weilin Zhang, Ying Liu, Luhua Lai
Human reticulocyte 15-lipoxygenase (15-LOX) plays an important role in inflammation resolution and is also involved in many cancer-related processes. Both an activator and an inhibitor will serve as research tools for understanding the biological functions of 15-LOX and provide opportunities for drug discovery. In a previous study, both allosteric activators and inhibitors of 15-LOX were discovered through a virtual screening based computational approach. However, why molecules binding to the same site causes different effects remains to be disclosed...
May 21, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29772700/inhibition-of-arachidonate-12-15-lipoxygenase-improves-%C3%AE-galactosidase-efficacy-in-ipsc-derived-cardiomyocytes-from-fabry-patients
#2
Yueh Chien, Shih-Jie Chou, Yuh-Lih Chang, Hsin-Bang Leu, Yi-Ping Yang, Ping-Hsing Tsai, Ying-Hsiu Lai, Kuan-Hsuan Chen, Wei-Chao Chang, Shih-Hsien Sung, Wen-Chung Yu
(1) Background: A high incidence of intervening sequence (IVS)4+919 G>A mutation with later-onset cardiac phenotype have been reported in a majority of Taiwan Fabry cohorts. Some evidence indicated that conventional biomarkers failed to predict the long-term progression and therapeutic outcome; (2) Methods: In this study, we constructed an induced pluripotent stem cell (iPSC)-based platform from Fabry cardiomyopathy (FC) patients carrying IVS4+919 G>A mutation to screen for potential targets that may help the conventional treatment; (3) Results: The FC-patient-derived iPSC-differentiated cardiomyocytes (FC-iPSC-CMs) carried an expected IVS4+919 G>A genetic mutation and recapitulated several FC characteristics, including low α-galactosidase A enzyme activity and cellular hypertrophy...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29763661/prominent-release-of-lipoxygenase-generated-mediators-in-a-murine-house-dust-mite-induced-asthma-model
#3
Johan Kolmert, Sergio Piñeiro-Hermida, Craig E Wheelock, Mats Hamberg, Joshua A Gregory, Icíar P López, Alexander Fauland, Sven-Erik Dahlén, José G Pichel, Mikael Adner
The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers. Of the 112 screened LMs, 26 were increased between 2 to >25-fold in BALF with HDM treatment (p < 0...
May 12, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29760648/profile-of-arachidonic-acid-derived-inflammatory-markers-and-its-modulation-by-nitro-oleic-acid-in-an-inherited-model-of-amyotrophic-lateral-sclerosis
#4
Andrés Trostchansky, Mauricio Mastrogiovanni, Ernesto Miquel, Sebastián Rodríguez-Bottero, Laura Martínez-Palma, Patricia Cassina, Homero Rubbo
The lack of current treatments for amyotrophic lateral sclerosis (ALS) highlights the need of a comprehensive understanding of the biological mechanisms of the disease. A consistent neuropathological feature of ALS is the extensive inflammation around motor neurons and axonal degeneration, evidenced by accumulation of reactive astrocytes and activated microglia. Final products of inflammatory processes may be detected as a screening tool to identify treatment response. Herein, we focus on (a) detection of arachidonic acid (AA) metabolization products by lipoxygenase (LOX) and prostaglandin endoperoxide H synthase in SOD1G93A mice and (b) evaluate its response to the electrophilic nitro-oleic acid (NO2 -OA)...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29739755/erv1-chemr23-signaling-protects-from-atherosclerosis-by-modifying-oxldl-uptake-and-phagocytosis-in-macrophages
#5
Andres Laguna-Fernandez, Antonio Checa, Miguel Carracedo, Gonzalo Artiach, Marcelo H Petri, Roland Baumgartner, Maria J Forteza, Xintong Jiang, Teodora Andonova, Mary E Walker, Jesmond Dalli, Hildur Arnardottir, Anton Gisterå, Silke Thul, Craig E Wheelock, Gabrielle Paulsson-Berne, Daniel F J Ketelhuth, Göran K Hansson, Magnus Bäck
Background -In addition to enhanced pro-inflammatory signaling, impaired resolution of vascular inflammation plays a key role in atherosclerosis. Pro-resolving lipid mediators formed through the 12/15 lipoxygenase pathways exert protective effects against murine atherosclerosis. n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), serve as the substrate for the formation of lipid mediators, which transduce potent anti-inflammatory and pro-resolving actions through their cognate G-protein-coupled receptors...
May 8, 2018: Circulation
https://www.readbyqxmd.com/read/29684557/regiospecificity-of-a-novel-bacterial-lipoxygenase-from-myxococcus-xanthus-for-polyunsaturated-fatty-acids
#6
Jung-Ung An, Seung-Hye Hong, Deok-Kun Oh
Lipoxygenase (LOX) is the key enzyme involved in the synthesis of oxylipins as signaling compounds that are important for cell growth and development, inflammation, and pathogenesis in various organisms. The regiospecificity of LOX from Myxococcus xanthus, a gram-negative bacterium, was investigated. The enzyme catalyzed oxygenation at the n-9 position in C20 and C22 polyunsaturated fatty acids (PUFAs) to form 12S- and 14S-hydroxy fatty acids (HFAs), respectively, and oxygenation at the n-6 position in C18 PUFAs to form 13-HFAs...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29681254/dietary-resveratrol-impairs-body-weight-gain-due-to-reduction-of-feed-intake-without-affecting-fatty-acid-composition-in-atlantic-salmon
#7
D Menoyo, G Kühn, N Ruiz-Lopez, K Pallauf, I Stubhaug, J J Pastor, I R Ipharraguerre, G Rimbach
Recent studies suggest that the use of vegetable oils at expense of fish oil in aquaculture feeds might have potential negative effects on fish redox homeostasis and adiposity. Resveratrol (RESV) is a lipid-soluble phytoalexin present in fruits and vegetables with proven in vivo antioxidant function in animals. The present study aims to assess the potential use of RESV in Atlantic salmon feeds. To this end, post-smolt salmons with an initial BW of 148±3 g were fed four experimental diets for 15 weeks. A diet low in fish oil served as a control and was supplemented with 0, 0...
April 23, 2018: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29627380/12-15-lipoxygenase-a-crucial-enzyme-in-diverse-types-of-cell-death
#8
REVIEW
Qiu-Qi Li, Qin-Li, Ji-Ning Jia, Zhao-Qian Liu, Hong-Hao Zhou, Xiao-Yuan Mao
The 12/15-lipoxygenase (12/15-LOX) enzymes react with polyunsaturated fatty acids producing active lipid metabolites that are involved in plethora of human diseases including neurological disorders. A great many of elegant studies over the last decades have contributed to unraveling the mechanism how 12/15-lipoxygenase play a role in these diseases. And the way it works is mainly through apoptosis. However, recent years have found that the way 12/15-lipoxygenase works is also related to autophagy and ferroptosis, a newly defined type of cell death by Stockwell's lab in 2012...
April 5, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29625273/botany-ethnomedicines-phytochemistry-and-pharmacology-of-himalayan-paeony-paeonia-emodi-royle
#9
REVIEW
Mushtaq Ahmad, Khafsa Malik, Akash Tariq, Guolin Zhang, Ghulam Yaseen, Neelam Rashid, Shazia Sultana, Muhammad Zafar, Kifayat Ullah, Muhammad Pukhtoon Zada Khan
ETHNOPHARMACOLOGICAL RELEVANCE: Himalayan paeony (Paeonia emodi Royle.) is an important species used to treat various diseases. This study aimed to compile the detailed traditional medicinal uses, phytochemistry, pharmacology and toxicological investigations on P. emodi. This study also highlights taxonomic validity, quality of experimental designs and shortcomings in previously reported information on Himalayan paeony. METHODS: The data was extracted from unpublished theses (Pakistan, China, India and Nepal), and different published research articles confined to pharmacology, phytochemistry and antimicrobial activities using different databases through specific keywords...
April 3, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29624122/docking-steered-molecular-dynamics-and-qsar-studies-as-strategies-for-studying-isoflavonoids-as-5-12-and-15-lipoxygenase-inhibitors
#10
Francisco Cabezas, Carolina Mascayano
Lipoxygenases (LOX) are enzymes that catalyze polyunsaturated fatty acid peroxidation and have a non-heme iron atom located in their active site. They are implicated in the arachidonic acid pathway and involved in inflammation, fever, pain production and in the origins of several diseases such as cancer, asthma and psoriasis. The search for inhibitors of these enzymes has emerged in the last years, and isoflavonoids have a broad spectrum of biological activity with low cytotoxicity. Our previous results have shown that isoflavonoids inhibited different LOX isoforms in vitro...
April 6, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29605541/activation-of-the-12-15-lipoxygenase-pathway-accompanies-metabolic-decline-in-db-db-pre-diabetic-mice
#11
Anca D Dobrian, Ryan W Huyck, Lindsey Glenn, Vijay Gottipati, Bronson A Haynes, Göran I Hansson, Anna Marley, William L McPheat, Jerry L Nadler
The 12-lipoxygenase (12LO) pathway is a promising target to reduce islet dysfunction, adipose tissue (AT) inflammation and insulin resistance. Optimal pre-clinical models for the investigation of selective12LO inhibitors in this context have not yet been identified. The objective of this study was to characterize the time course of 12LO isoform expression and metabolite production in pancreatic islets and AT of C57BLKS/J-db/db obese diabetic mouse in a pre-diabetic state in order to establish a suitable therapeutic window for intervention with selective lipoxygenase inhibitors...
March 29, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29559341/biosynthesis-of-d-series-resolvins-in-skin-provides-insights-into-their-role-in-tissue-repair
#12
Jason Hellmann, Brian E Sansbury, Blenda Wong, Xiaofeng Li, Mansher Singh, Kristo Nuutila, Nan Chiang, Elof Eriksson, Charles N Serhan, Matthew Spite
Cutaneous injury causes underlying tissue damage that must be quickly repaired to minimize exposure to pathogens and to restore barrier function. While the role of growth factors in tissue repair is established, the role of lipid mediators in skin repair has not been extensively investigated. Using a mass spectrometry-based lipid mediator metabolomics approach, we identified D-series resolvins and related pro-resolving lipid mediators during skin injury in mice and pigs. Differentiation of human epidermal keratinocytes increased expression of 15-lipoxygenase and stereospecific production of 17S-hydroxydocosahexaenoic acid, the common upstream biosynthetic marker and precursor of D-series resolvins...
March 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29555013/pinosylvin-exacerbates-lps-induced-apoptosis-via-alox-15-upregulation-in-leukocytes
#13
Ohseong Kwon, Youngsik Seo, Heonyong Park
Pinosylvin is known to have anti-inflammatory activity in endothelial cells. In this study, we found that pinosylvin had a pro-apoptotic activity in lipopolysaccharide (LPS)-preconditioned leukocytes. This finding suggests that pinosylvin has an effect on the resolution of inflammation. To understand the detailed mechanism, we examined if pinosylvin enhances cyclooxygenase (COX) or lipoxygenase (LOX) activity in THP-1 and U937 cells. LOX activity was found to be markedly increased by pinosylvin, whereas COX activity was not altered...
March 20, 2018: BMB Reports
https://www.readbyqxmd.com/read/29550533/novel-n-substituted-5-aminosalicylamides-as-dual-inhibitors-of-cyclooxygenase-and-5-lipoxygenase-enzymes-synthesis-biological-evaluation-and-docking-study
#14
Mohamed K S El-Nagar, Hajjaj H M Abdu-Allah, Ola I A Salem, Abdel-Hamid N Kafafy, Hanan S M Farghaly
Three new series of 5-aminosalicylic acid derivatives; series I (14, 16-18), series II (19-30) and series III (31-41) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1 H NMR, 13 C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval...
March 6, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29546268/pharmacological-inhibition-of-arachidonate-15-lipoxygenase-alox15-protects-human-spermatozoa-against-oxidative-stress
#15
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
https://www.readbyqxmd.com/read/29545796/macrophage-derived-protein-s-facilitates-apoptotic-polymorphonuclear-cell-clearance-by-resolution-phase-macrophages-and-supports-their-reprogramming
#16
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
https://www.readbyqxmd.com/read/29526491/genetic-deletion-of-12-15-lipoxygenase-promotes-effective-resolution-of-inflammation-following-myocardial-infarction
#17
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...
May 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29501481/cymbopogon-citratus-and-cymbopogon-giganteus-essential-oils-have-cytotoxic-effects-on-tumor-cell-cultures-identification-of-citral-as-a-new-putative-anti-proliferative-molecule
#18
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...
March 6, 2018: Biochimie
https://www.readbyqxmd.com/read/29474901/arachidonic-acid-metabonomics-study-for-understanding-therapeutic-mechanism-of-huo-luo-xiao-ling-dan-on-rat-model-of-rheumatoid-arthritis
#19
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...
May 10, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29472381/deactivation-of-12-s-hete-through-%C3%AF-1-hydroxylation-and-%C3%AE-oxidation-in-alternatively-activated-macrophages
#20
Tamas Kriska, Michael J Thomas, John R Falck, William B Campbell
Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (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...
April 2018: Journal of Lipid Research
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