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Autotaxin

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https://www.readbyqxmd.com/read/29147686/lipoprotein-a-associated-molecules-are-prominent-components-in-plasma-and-valve-leaflets-in-calcific-aortic-valve-stenosis
#1
Michael Torzewski, Amir Ravandi, Calvin Yeang, Andrea Edel, Rahul Bhindi, Stefan Kath, Laura Twardowski, Jens Schmid, Xiaohong Yang, Ulrich F W Franke, Joseph L Witztum, Sotirios Tsimikas
The LPA gene is the only monogenetic risk factor for calcific aortic valve stenosis (CAVS). Oxidized phospholipids (OxPL) and lysophosphatidic acid generated by autotaxin (ATX) from OxPL are pro-inflammatory. Aortic valve leaflets were categorized pathologically from Both ATX-apoB and ATX-apo(a) were measureable in plasma. Lp(a), autotaxin, OxPL and MDA epitopes progressively increased in immunostaining (p<0.001 for all). Six species of OxPL and LysoPA were identified following extraction from valve leaflets...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29114991/serum-autotaxin-is-a-useful-liver-fibrosis-marker-in-patients-with-chronic-hepatitis-b-virus-infection
#2
Satoru Joshita, Yuki Ichikawa, Takeji Umemura, Yoko Usami, Ayumi Sugiura, Soichiro Shibata, Tomoo Yamazaki, Naoyuki Fujimori, Michiharu Komatsu, Akihiro Matsumoto, Koji Igarashi, Masao Ota, Eiji Tanaka
BACKGROUND AND AIMS: Autotaxin (ATX) is a secreted enzyme that is considered to be associated with liver damage as well as fibrosis. This study assessed the ability of ATX to diagnose liver fibrosis in patients with chronic hepatitis B virus (HBV) infection. METHODS: Serum ATX levels were retrospectively evaluated in 101 treatment-naïve patients with HBV-related chronic hepatitis or cirrhosis all of whom had undergone liver biopsy at our hospital. RESULTS: Serum ATX concentration increased significantly according to liver fibrosis stage in overall (r = 0...
November 8, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29065699/annals-express-performance-of-autotaxin-as-a-serum-marker-of-liver-fibrosis
#3
Hitoshi Ikeda, Mariko Kobayashi, Hiromitsu Kumada, Kenichiro Enooku, Kazuhiko Koike, Makoto Kurano, Masaya Sato, Takahiro Nojiri, Tamaki Kobayashi, Ryunosuke Ohkawa, Satoshi Shimamoto, Koji Igarashi, Junken Aoki, Yutaka Yatomi
BACKGROUND: Because autotaxin (ATX) reportedly has a better performance than hyaluronic acid (HA) as a marker of liver fibrosis for the prediction of cirrhosis caused by hepatitis C, we aimed to further evaluate the role of ATX in liver fibrosis of other etiologies. METHODS: ATX antigen was measured in serum samples from 108 patients with chronic hepatitis B and 128 patients with non-alcoholic fatty liver disease (NAFLD) who had undergone a liver biopsy as well as healthy subjects and patients with chronic kidney disease (CKD), diabetes mellitus (DM), rheumatoid arthritis (RA) and cardiac dysfunction (CD)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/29058512/maternal-serum-autotaxin-levels-in-early-and-late-onset-preeclampsia
#4
Hakan Erenel, Nevin Yilmaz, Tayfur Cift, Berk Bulut, Isik Sozen, Berna Aslan Cetin, Altay Gezer, Hakan Ekmekci, Baris Kaya, Abdullah Tuten
PURPOSE: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital. METHODS: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients...
November 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/29028570/bovine-ovarian-follicular-growth-and-development-correlate-with-lysophosphatidic-acid-expression
#5
Emilia Sinderewicz, Katarzyna Grycmacher, Dorota Boruszewska, Ilona Kowalczyk-Zięba, Joanna Staszkiewicz, Tomasz Ślężak, Izabela Woclawek-Potocka
The basis of successful reproduction is proper ovarian follicular growth and development. In addition to prostaglandins and vascular endothelial growth factor, a number of novel factors are suggested as important regulators of follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This study focuses on examining the expression of these factors in granulosa and thecal cells that originate from different ovarian follicle types and their link with the expression of lysophosphatidic acid (LPA), known local regulator of reproductive functions in the cow...
September 25, 2017: Theriogenology
https://www.readbyqxmd.com/read/28968864/atm-activated-autotaxin-atx-propagates-inflammation-and-dna-damage-in-lung-epithelial-cells-a-new-mode-of-action-for-silica-induced-dna-damage
#6
Huiyuan Zheng, Johan Högberg, Ulla Stenius
Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16HBE lung epithelial cells were exposed silica particles. Reactive oxidative species (ROS), NLRP3 inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were endpoints...
September 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28931042/evaluation-of-the-cytotoxicity-of-the-bithionol-paclitaxel-combination-in-a-panel-of-human-ovarian-cancer-cell-lines
#7
Vijayalakshmi N Ayyagari, Paula L Diaz-Sylvester, Tsung-Han Jeff Hsieh, Laurent Brard
Previously, Bithionol (BT) was shown to enhance the chemosensitivity of ovarian cancer cell lines to cisplatin treatment. In the present study, we focused on the anti-tumor potential of the BT-paclitaxel combination when added to a panel of ovarian cancer cell lines. This in vitro study aimed to 1) determine the optimum schedule for combination of BT and paclitaxel and 2) assess the nature and mechanism(s) underlying BT-paclitaxel interactions. The cytotoxic effects of both drugs either alone or in combination were assessed by presto-blue cell viability assay using six human ovarian cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28922661/lysophosphatidic-acid-inhibits-insulin-signaling-in-primary-rat-hepatocytes-via-the-lpa3-receptor-subtype-and-is-increased-in-obesity
#8
Susann Fayyaz, Lukasz Japtok, Fabian Schumacher, Dominik Wigger, Tim Julius Schulz, Kathrin Haubold, Erich Gulbins, Heinz Völler, Burkhard Kleuser
BACKGROUND/AIMS: Obesity is a main risk factor for the development of hepatic insulin resistance and it is accompanied by adipocyte hypertrophy and an elevated expression of different adipokines such as autotaxin (ATX). ATX converts lysophosphatidylcholine to lysophosphatidic acid (LPA) and acts as the main producer of extracellular LPA. This bioactive lipid regulates a broad range of physiological and pathological responses by activation of LPA receptors (LPA1-6). METHODS: The activation of phosphatidylinositide 3-kinases (PI3K) signaling (Akt and GSK-3ß) was analyzed via western blotting in primary rat hepatocytes...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28874440/blocking-gp130-signaling-suppresses-autotaxin-expression-in-adipocytes-and-improves-insulin-sensitivity-in-diet-induced-obesity
#9
Shuhong Sun, Ran Wang, Jianwen Song, Ming Guan, Na Li, Xiaotian Zhang, Zhenwen Zhao, Junjie Zhang
Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine. Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Upregulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that glycoprotein 130 (gp130)-mediated Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) activation was required for abundant ATX expression in adipocytes...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28871044/lpp3-mediates-self-generation-of-chemotactic-lpa-gradients-by-melanoma-cells
#10
Olivia Susanto, Yvette W H Koh, Nick Morrice, Sergey Tumanov, Peter A Thomason, Matthew Nielson, Luke Tweedy, Andrew J Muinonen-Martin, Jurre J Kamphorst, Gillian M Mackay, Robert H Insall
Melanoma cells steer out of tumours using self-generated lysophosphatidic acid (LPA) gradients. The cells break down LPA, which is present at high levels around the tumours, creating a dynamic gradient that is low in the tumour and high outside. They then also migrate up this gradient, creating a complex and evolving outward chemotactic stimulus. Here we introduce a new assay for self-generated chemotaxis, and show that raising LPA levels causes a delay in migration rather than loss of chemotactic efficiency...
September 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28816078/pathobiology-of-lp-a-in-calcific-aortic-valve-disease
#11
Patrick Mathieu, Benoit J Arsenault, Marie-Chloé Boulanger, Yohan Bossé, Marlys L Koschinsky
Calcific aortic valve disease (CAVD) is the most prevalent heart valve disorder. Gene variant in the LPA gene, which encodes for apolipoprotein(a), has been associated at the genome-wide level with CAVD. The process whereby Lp(a) promotes the development of CAVD is under intensive investigation and recent data have shed important insights into disease biology. In this regard, autotaxin (ATX), a lysophospholipase D, interacts with Lp(a) and promotes the mineralization of the aortic valve. Areas covered: In this paper, we are reviewing the biology of Lp(a) and the latest discoveries about the molecular processes that link this lipoprotein with the development of CAVD including the role of ATX...
August 24, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28811491/high-fat-diet-induced-acceleration-of-osteoarthritis-is-associated-with-a-distinct-and-sustained-plasma-metabolite-signature
#12
Poulami Datta, Yue Zhang, Alexa Parousis, Anirudh Sharma, Evgeny Rossomacha, Helal Endisha, Brian Wu, Izabela Kacprzak, Nizar N Mahomed, Rajiv Gandhi, Jason S Rockel, Mohit Kapoor
Metabolic changes induced by high fat diet (HFD) that contribute to osteoarthritis (OA) are poorly understood. We investigated longitudinal changes to metabolites and their contribution to OA pathogenesis in response to HFD. HFD-fed mice exhibited acceleration of spontaneous age-related and surgically-induced OA compared to lean diet (LD)-fed mice. Using metabolomics, we identified that HFD-fed mice exhibited a distinct and sustained plasma metabolite signature rich in phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPCs), even after resumption of normal chow diet...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743508/design-synthesis-docking-and-biological-evaluation-of-4-phenyl-thiazole-derivatives-as-autotaxin-atx-inhibitors
#13
Anand Balupuri, Dae-Yon Lee, Myeong Hwi Lee, Sangeun Chae, Eunmi Jung, Yunki Kim, Jeonghee Ryu, Nam Sook Kang
The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is involved in several human diseases such as cancer, autoimmune diseases, inflammatory diseases neurodegenerative diseases and fibrotic diseases. Herein, a series of 4-phenyl-thiazole based compounds was designed and synthesized. Compounds were evaluated for their ATX inhibitory activity using FS-3 and human plasma assays. In the FS-3 assay, compounds 20 and 21 significantly inhibited the ATX at low nanomolar level (IC50=2.99 and 2.19nM, respectively)...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-an-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#14
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Sameh Soror, Jan Steyaert, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28687529/design-synthesis-and-biological-evaluation-of-2-4-dihydropyrano-2-3-c-pyrazole-derivatives-as-autotaxin-inhibitors
#15
Tatu Pantsar, Prosanta Singha, Tapio J Nevalainen, Igor Koshevoy, Jukka Leppänen, Antti Poso, Juha M A Niskanen, Sanna Pasonen-Seppänen, Juha R Savinainen, Tuomo Laitinen, Jarmo T Laitinen
Inhibition of Autotaxin (ATX) is a potential treatment strategy for several diseases, including tumors with elevated ATX-lysophosphatidic acid (LPA) signaling. Combining structure-based virtual screening together with hen egg-white Autotaxin (ewATX) activity assays enabled the discovery of novel small-molecule ATX inhibitors with a 2,4-dihydropyrano[2,3-c]pyrazole scaffold. These compounds are suggested to bind to the lipophilic pocket, leaving the active site unrestrained. Our most potent compound, (S)-6-amino-4-(3,4-dichlorophenyl)-3-(4-[(4-fluorobenzyl)oxy]phenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile [(S)-25], inhibited human ATX (hATX) with an IC50-value of 134nM...
July 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28674249/effects-of-gintonin-enriched-fraction-in-an-atopic-dermatitis-animal-model-involvement-of-autotaxin-regulation
#16
Byung-Hwan Lee, Ho-Kyoung Kim, Minhee Jang, Hyeon-Joong Kim, Sun-Hye Choi, Sung-Hee Hwang, Hyoung-Chun Kim, Hyewhon Rhim, Ik-Hyun Cho, Seung-Yeol Nah
Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C18 : 2 with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28667502/lysophosphatidic-acid-protects-against-endotoxin-induced-acute-kidney-injury
#17
Koryun Mirzoyan, Colette Denis, Audrey Casemayou, Marion Gilet, Dimitri Marsal, Dominique Goudounéche, Stanislas Faguer, Jean-Loup Bascands, Joost P Schanstra, Jean-Sébastien Saulnier-Blache
Septic shock is the most common cause of acute kidney injury (AKI), but the underlying mechanisms remain unclear and no targeted therapies exist. Lysophosphatidic acid (LPA) is a bioactive lipid which in vivo administration was reported to mitigate inflammation and injuries caused by bacterial endotoxemia in the liver and lung. The objective of the present study was to determine whether LPA can protect against sepsis-associated AKI. C57BL/6 mice were treated with LPA 18:1 (5 mg/kg, i.p.) 1 h before being injected with the endotoxin lipopolysaccharide (LPS), and AKI was evaluated after 24 h...
June 30, 2017: Inflammation
https://www.readbyqxmd.com/read/28654680/serum-fatty-acid-binding-protein-4-fabp4-concentration-is-associated-with-insulin-resistance-in-peripheral-tissues-a-clinical-study
#18
Risa Nakamura, Tsuyoshi Okura, Yohei Fujioka, Keisuke Sumi, Kazuhiko Matsuzawa, Shoichiro Izawa, Etsuko Ueta, Masahiko Kato, Shin-Ichi Taniguchi, Kazuhiro Yamamoto
Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28642310/metabolomics-analysis-identifies-sex-associated-metabotypes-of-oxidative-stress-and-the-autotaxin-lysopa-axis-in%C3%A2-copd
#19
Shama Naz, Johan Kolmert, Mingxing Yang, Stacey N Reinke, Muhammad Anas Kamleh, Stuart Snowden, Tina Heyder, Bettina Levänen, David J Erle, C Magnus Sköld, Åsa M Wheelock, Craig E Wheelock
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform...
June 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28616586/the-autotaxin-lysophosphatidic-acid-pathway-emerges-as-a-therapeutic-target-to-prevent-liver-cancer
#20
Derek J Erstad, Andrew M Tager, Yujin Hoshida, Bryan C Fuchs
Using transcriptome meta-analysis, we recently identified the autotaxin (ATX)-lysophosphatidic acid (LPA) pathway as a regulator of hepatocellular carcinoma (HCC) risk in human cirrhosis patients. Pharmacological targeting of this pathway reduced fibrosis progression and HCC development in animals, identifying ATX-LPA signaling as a novel chemoprevention strategy for cirrhosis and HCC.
2017: Molecular & Cellular Oncology
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