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15 lipoxygenase

Ganesh V Halade, Vasundhara Kain, Laurence M Black, Sumanth D Prabhu, Kevin A Ingle
Post-myocardial infarction (MI), overactive inflammation is the hallmark of aging, however, the mechanism is unclear. We hypothesized that excess influx of omega 6 fatty acids may impair resolution, thus impacting the cardiosplenic and cardiorenal network post-MI. Young and aging mice were fed on standard lab chow (LC) and excess fatty acid (safflower oil; SO)-enriched diet for 2 months and were then subjected to MI surgery. Despite similar infarct areas and left ventricle (LV) dysfunction post-MI, splenic mass spectrometry data revealed higher levels of arachidonic acid (AA) derived pro-inflammatory metabolites in young-SO, but minimal formation of docosanoids, D- and E- series resolvins in SO-fed aged mice...
October 18, 2016: Aging
Mayuko Morita, Yuji Naito, Toshikazu Yoshikawa, Etsuo Niki
With increasing evidence showing the involvement of oxidative stress in the pathogenesis of various diseases, the effects of clinical drugs possessing antioxidant functions have received much attention. The unregulated oxidative modification of biological molecules leading to diseases is mediated by multiple oxidants including free radicals, peroxynitrite, hypochlorite, lipoxygenase, and singlet oxygen. The capacity of antioxidants to scavenge or quench oxidants depends on the nature of oxidants. In the present study, the antioxidant effects of several clinical drugs against plasma lipid oxidation induced by the aforementioned five kinds of oxidants were investigated from the production of lipid hydroperoxides, which have been implicated in the pathogenesis of various diseases...
October 13, 2016: Bioorganic & Medicinal Chemistry Letters
Ruobing Xu, Shu Wang, Weishan Li, Zhen Liu, Jiaxin Tang, Xiaobo Tang
OBJECTIVE In this study, the authors investigated the involvement of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in the regulation of peroxisome proliferator-activated receptor-γ (PPARγ) after intracerebral hemorrhage (ICH) and its effects on hemorrhage-induced inflammatory response and oxidative stress in an experimental rodent model. METHODS To simulate ICH in a rat model, the authors injected autologous whole blood into the right striatum of male Sprague-Dawley rats. The distribution and expression of 12/15-lipoxygenase (12/15-LOX) were determined by immunohistochemistry and Western blot analysis, respectively...
October 14, 2016: Journal of Neurosurgery
Eleonora Cianci, Oriana Trubiani, Francesca Diomede, Ilaria Merciaro, Ida Meschini, Pantaleone Bruni, Fausto Croce, Mario Romano
Lipoxin (LX)A4 is a lipoxygenase-formed arachidonic acid metabolite with potent anti-inflammatory, pro-resolution properties. Its therapeutic efficacy has been largely demonstrated in a variety of cellular, preclinical and clinical models. Among these, periodontal disease, where LXA4 promotes tissue repair, also by modulating functions of human periodontal ligament stem cells (hPDLSCs). As medicated biomembranes may be particularly useful in clinical settings, where local stimulation of tissue repair is needed, we used electrospinning to embed LXA4 in membranes made of poly(ethylene oxide) (PEO) and poly(d,l-lactide) (PDLLA)...
October 11, 2016: International Journal of Pharmaceutics
Yang Ou, Shang-Jui Wang, Dawei Li, Bo Chu, Wei Gu
Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N(1)-acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Suku-Maran Shalini, Deron R Herr, Wei-Yi Ong
Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception...
October 1, 2016: Molecular Neurobiology
Jayashree A Chandrasekharan, Xiao M Huang, Alexandar Hwang, Neelam Sharma-Walia
: Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's Sarcoma (KS) and Primary Effusion Lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins...
September 28, 2016: Journal of Virology
Shin Kim, Kwang-Joon Jeong, Sung Kweon Cho, Joo-Won Park, Woo-Jae Park
Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM‑induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM‑induced cell death. Among several antioxidants, CA partially alleviated SM‑induced cell death in a dose‑dependent manner...
September 23, 2016: Molecular Medicine Reports
Midéko Justin Kohoude, Fernand Gbaguidi, Pierre Agbani, Marc-Abel Ayedoun, Sylvie Cazaux, Jalloul Bouajila
CONTEXT: Boswellia dalzielii Hutch. (Burseraceae) is an aromatic plant. The leaves are used for beverage flavouring. OBJECTIVE: This study investigates the chemical composition and biological activities of various extracts. MATERIALS AND METHODS: The essential oil was prepared via hydrodistillation. Identification and quantification were realized via GC-MS and GC-FID. Consecutive extractions (cyclohexane, dichloromethane, ethyl acetate and methanol) were carried out and various chemical groups (phenolics, flavonoids, tannins, antocyanins and sugar) were quantified...
September 21, 2016: Pharmaceutical Biology
Michelle Armstrong, Christopher van Hoorebeke, Thomas Horn, Joshua Deschamps, J Cody Freedman, Chakrapani Kalyanaraman, Matthew P Jacobson, Theodore Holman
Human 15-lipoxygenase-1 (h15-LOX-1 or h12/15-LOX) reacts with polyunsaturated fatty acids and produces bioactive lipid derivatives that are implicated in many important human diseases. One such disease is stroke, which is the fifth leading cause of death and the first leading cause of disability in America. The discovery of h15-LOX-1 inhibitors could potentially lead to novel therapeutics in the treatment of stroke, however, little is known about the inhibitor/active site interaction. This study utilizes site-directed mutagenesis, guided in part by molecular modeling, to gain a better structural understanding of inhibitor interactions within the active site...
November 1, 2016: Bioorganic & Medicinal Chemistry
Thuy Lan Nguyen, Anders Rusten, Mona Skogsrud Bugge, Karl Egil Malterud, Drissa Diallo, Berit Smestad Paulsen, Helle Wangensteen
ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium guineense has been traditionally used in Mali in West Africa for the treatment of different diseases such as stomach problems, wounds, inflammations and various female disorders. AIMS OF THE STUDY: (1) To perform an ethnopharmacological survey on the traditional use of S. guineense among Malian healers. (2) To isolate and identify chemical constituents from S. guineense leaves and to study their radical scavenging and enzyme inhibitory effects...
November 4, 2016: Journal of Ethnopharmacology
Xiaomin Liu, Lijing Hou, Weiwei Huang, Yuan Gao, Xin Lv, Jiyou Tang
OBJECTIVE: lncRNAs are recently thought to play a significant role in cellular homeostasis during pathological process of diseases by competing inhibiting miRNA function. The aim of present study was to assess the function of long non-coding RNA (lncRNA) MEG3 and its functional interaction with microRNA-181b in cerebral ischemic infarct of mice and hypoxia-induced neurons apoptosis. METHODS: To address this question, we performed the experiments with in vivo middle cerebral artery occlusion (MCAO) mice model and in vitro oxygen-glucose deprivation (OGD)-cultured neuronal HT22 cell line...
2016: Frontiers in Cellular Neuroscience
Simone Hanna Brutsch, Marlena Rademacher, Sophia Regine Roth, Karin Muller, Susanne Eder, Dagmar Viertel, Christiane Franz, Hartmut Kuhn, Astrid Borchert
Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are antagonizing enzymes in the metabolism of hydroperoxy lipids. In spermatoid cells and/or in the male reproductive system both enzymes are apparently expressed and GPX4 serves as anti-oxidative enzyme but also as structural protein. In this study we explored whether germ-line inactivation of the Alox15 gene might rescue male subfertility induced by heterozygous expression of catalytically silent Gpx4. To address this question we employed Gpx4 knockin mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was replaced by a redox inactive alanine...
September 15, 2016: Journal of Biological Chemistry
Nikolaos Eleftheriadis, Stephanie A Thee, Martijn R H Zwinderman, Niek G J Leus, Frank J Dekker
Human 15-lipoxygenase-1 (15-LOX-1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity-based probes of 15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15-LOX-1 activity-based probe for the efficient activity-based labeling of recombinant 15-LOX-1. 15-LOX-1-dependent labeling in cell lysates and tissue samples was also possible...
September 26, 2016: Angewandte Chemie
Peng Zhang, Xin Xing, Chunxiao Hu, Hui Yu, Qian Dong, Guanglei Chang, Shu Qin, Jian Liu, Dongying Zhang
Statins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxylin and eosin (HE) staining showed that ALOX15 overexpression increased the thickness of the intima-media (IMT). Immunohistochemistry and western blotting showed that atorvastatin increased the expression of cellular adhesion molecules (CAMs) but decreased the expression of endothelial nitric oxide synthase (eNOS); these effects of atorvastatin were blocked by ALOX15 overexpression...
2016: Mediators of Inflammation
Pongsatorn Meesawatsom, James Burston, Gareth Hathway, Andrew Bennett, Victoria Chapman
BACKGROUND: Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects...
2016: Journal of Neuroinflammation
Xiaomin Ma, Hu Meng, Luhua Lai
Allostery is the phenomenon in which a ligand binding at one site affects other sites in the same macromolecule. Allostery has important roles in many biological processes. Theoretically, all nonfibrous proteins are potentially allosteric. However, few allosteric proteins have been validated, and the identification of novel allosteric sites remains a challenge. The motion of residues and subunits underlies protein function; therefore, we hypothesized that the motions of allosteric and orthosteric sites are correlated...
September 26, 2016: Journal of Chemical Information and Modeling
Katharina Dietz, Marta de Los Reyes Jiménez, Eva S Gollwitzer, Adam M Chaker, Ulrich M Zissler, Olof P Rådmark, Hoeke A Baarsma, Melanie Königshoff, Carsten B Schmidt-Weber, Benjamin J Marsland, Julia Esser-von Bieren
BACKGROUND: Airway remodeling is a detrimental and refractory process showing age-dependent clinical manifestations, which are mechanistically undefined. The leukotriene (LT) and wingless/ integrase (Wnt) pathways have been implicated in remodeling, but age-specific expression profiles and common regulators remained elusive. OBJECTIVE: We sought to study the activation of the LT and Wnt pathways during early- or late-onset allergic airway inflammation and to address regulatory mechanisms and clinical relevance in normal human bronchial epithelial cells (NHBEs) and nasal polyp tissues...
August 20, 2016: Journal of Allergy and Clinical Immunology
Ishaku Leo Elisha, Jean-Paul Dzoyem, Lyndy Joy McGaw, Francien S Botha, Jacobus Nicolaas Eloff
BACKGROUND: Oxidative stress predisposes the human and animal body to diseases like cancer, diabetes, arthritis, rheumatoid arthritis, atherosclerosis and chronic inflammatory disorders. Hence, this study seeks to determine the antioxidant, anti-inflammatory and anti-arthritic activities of acetone leaf extracts of nine South African medicinal plants that have been used traditionally to treat arthritis and inflammation. METHODS: The anti-inflammatory activity of the extracts was determined by investigating inhibition of nitric oxide production in lipopolysaccharide activated RAW 264...
2016: BMC Complementary and Alternative Medicine
Annika Lundqvist, Mikael Sandstedt, Joakim Sandstedt, Ruth Wickelgren, Göran I Hansson, Anders Jeppsson, Lillemor Mattsson Hultén
Ischemic heart disease is a major cause of death and morbidity and the search for novel therapeutic targets is still required. We have previously shown that the enzyme arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), is highly expressed in ischemic heart tissue, but its role in the pathogenesis of ischemic heart disease is unclear. Here we showed that expression of ALOX15, but not ALOX12 or ALOX15B, was increased in ischemic versus non-ischemic human heart biopsy samples...
2016: PloS One
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