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Autotaxin

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https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#1
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29774420/lysophosphatidylcholine-as-a-predictor-of-postoperative-complications-after-colorectal-cancer-surgery
#2
Akihisa Matsuda, Marina Yamada, Satoshi Matsumoto, Nobuyuki Sakurazawa, Takeshi Yamada, Takeshi Matsutani, Masao Miyashita, Eiji Uchida
PURPOSE: Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC). METHODS: The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7...
May 17, 2018: Surgery Today
https://www.readbyqxmd.com/read/29743582/synaptic-phospholipids-as-a-new-target-for-cortical-hyperexcitability-and-e-i-balance-in-psychiatric-disorders
#3
Carine Thalman, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, Torfi Sigrudsson, Maria Jelena Hauser, Stefan Tenzer, Ute Distler, Junken Aoki, Andrew J Morris, Gerd Geisslinger, Jochen Röper, Sergei Kirischuk, Heiko J Luhmann, Konstantin Radyushkin, Robert Nitsch, Johannes Vogt
Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses...
May 9, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29724718/the-autotaxin-lysophosphatidic-acid-axis-promotes-lung-carcinogenesis
#4
Christiana Magkrioti, Nikos Oikonomou, Eleanna Kaffe, Marios-Angelos Mouratis, Nikos Xylourgidis, Iliana Barbayianni, Petros Megadoukas, Vaggelis Harokopos, Christos Valavanis, Jerold Chun, Alexandra Kosma, Georgios T Stathopoulos, Evangelos Bouros, Demosthenes Bouros, Konstantinos N Syrigos, Vassilis Aidinis
Pathogenesis and progression of lung cancer (LC) are governed by complex interactions between the environment and host genetic susceptibility, which is further modulated by genetic and epigenetic changes. Autotaxin (ATX, ENPP2) is a secreted glycoprotein that catalyzes the extracellular production of lysophosphatidic acid (LPA), a growth-factor-like phospholipid which is further regulated by phospholipid phosphatases (PLPP). LPA's pleiotropic effects in almost all cell types are mediated through at least six, G-protein coupled LPA receptors (LPAR) that exhibit overlapping specificities, widespread distribution, and differential expression profiles...
May 3, 2018: Cancer Research
https://www.readbyqxmd.com/read/29704003/pilot-study-with-ibat-inhibitor-a4250-for-the-treatment-of-cholestatic-pruritus-in-primary-biliary-cholangitis
#5
Samer Al-Dury, Annika Wahlström, Staffan Wahlin, Jacqueline Langedijk, Ronald Oude Elferink, Marcus Ståhlman, Hanns-Ulrich Marschall
Pruritus is a common complication of cholestatic liver diseases. Inhibition of the ileal bile acid transporter (IBAT/ASBT) may emerge as treatment option. Our aim was to assess tolerability and effect on pruritus of the selective IBAT inhibitor A4250 in patients with primary biliary cholangitis (PBC). Ten patients with PBC and bile acid sequestrant treatment of cholestatic pruritus were after a two-week wash out of the bile acid sequestrant treated with either 0.75 mg (n = 4) or 1.5 mg (n = 5) of A4250 for four weeks...
April 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29677358/lysophosphatidic-acid-induces-ecm-production-via-activation-of-the-mechanosensitive-yap-taz-transcriptional-pathway-in-trabecular-meshwork-cells
#6
Leona T Y Ho, Nikolai Skiba, Christoph Ullmer, Ponugoti Vasantha Rao
Purpose: Lysophosphatidic acid (LPA), a bioactive lipid, has been shown to increase resistance to aqueous humor outflow (AH) through the trabecular meshwork (TM). The molecular basis for this response of the TM to LPA, however, is not completely understood. In this study, we explored the possible involvement of mechanosensitive Yes-associated protein (YAP) and its paralog, transcriptional coactivator with PDZ-binding domain (TAZ), transcriptional activation in extracellular matrix (ECM) production by LPA-induced contractile activity in human TM cells (HTM)...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29672037/correction-to-discovery-structure-activity-relationship-and-binding-mode-of-an-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#7
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
No abstract text is available yet for this article.
April 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29663077/is-patient-reported-outcome-improved-by-nalfurafine-hydrochloride-in-patients-with-primary-biliary-cholangitis-and-refractory-pruritus-a-post-marketing-single-arm-prospective-study
#8
Minami Yagi, Atsushi Tanaka, Tadashi Namisaki, Atsushi Takahashi, Masanori Abe, Akira Honda, Yasushi Matsuzaki, Hiromasa Ohira, Hitoshi Yoshiji, Hajime Takikawa
BACKGROUND: Patients with primary biliary cholangitis (PBC) frequently suffer from pruritus, which can severely impair their health-related quality of life (HRQOL). Nalfurafine hydrochloride, a selective κ-opioid receptor agonist, was recently approved in Japan for refractory pruritus in patients with chronic liver diseases, but it still remains unclear whether this treatment improves the patient-reported outcome (PRO) in PBC patients with refractory pruritus. Herein, we conducted a multicenter, post-marketing, single-arm prospective study to investigate the efficacy of nalfurafine in terms of PRO, and the associations of the efficacy with any clinical characteristics...
April 16, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29660533/role-of-lysophosphatidic-acid-in-the-retinal-pigment-epithelium-and-photoreceptors
#9
Grace E Lidgerwood, Andrew J Morris, Alison Conquest, Maciej Daniszewski, Louise A Rooney, Shiang Y Lim, Damián Hernández, Helena H Liang, Penelope Allen, Paul P Connell, Robyn H Guymer, Alex W Hewitt, Alice Pébay
The human retina is a complex structure of organised layers of specialised cells that support the transmission of light signals to the visual cortex. The outermost layer of the retina, the retinal pigment epithelium (RPE) forms part of the blood retina barrier and is implicated in many retinal diseases. Lysophosphatidic acid (LPA) is a bioactive lipid exerting pleiotropic effects in various cell types, during development, normal physiology and disease. Its producing enzyme AUTOTAXIN (ATX) is highly expressed by the pigmented epithelia of the human eye, including the RPE...
April 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29621954/lpar2-and-lpar4-are-the-main-receptors-responsible-for-lpa-actions-in-ovarian-endometriotic-cysts
#10
Ilona Kowalczyk-Zieba, Izabela Woclawek-Potocka, Tomasz Wasniewski, Dorota Boruszewska, Katarzyna Grycmacher, Emilia Sinderewicz, Joanna Staszkiewicz, Slawomir Wolczynski
Endometriosis has been considered as an estrogen (E2)-dependent and progesterone (P4)-resistant disease. On the other hand, lysophosphatidic acid (LPA) has been suggested as a significant modulator of ovarian pathology, acting via both LPA levels and LPA receptor (LPAR) upregulation. Therefore, the objective of the present study was to evaluate LPA concentration as well as LPARs, autotaxin (ATX), and phospholipase A2 (PLA2) expression in ovarian endometriotic cysts and normal endometrium with correlation of the expression of E2 and P4 receptors in endometriotic cysts...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29620892/hydroxamic-acids-constitute-a-novel-class-of-autotaxin-inhibitors-that-exhibit-in-vivo-efficacy-in-a-pulmonary-fibrosis-model
#11
Aikaterini Nikolaou, Ioanna Ninou, Maroula G Kokotou, Eleanna Kaffe, Antreas Afantitis, Vassilis Aidinis, George Kokotos
Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) generating the lipid mediator lysophosphatidic acid (LPA). Both ATX and LPA are involved in various pathological inflammatory conditions, including fibrosis and cancer, and have attracted a great interest as medicinal targets over the last decade. Thus, the development of novel potent ATX inhibitors is of great importance. We have developed a novel class of ATX inhibitors containing the zinc binding functionality of hydroxamic acid. Such novel hydroxamic acids, that incorporate a non-natural δ-amino acid residue, exhibit high in vitro inhibitory potency over ATX (IC50 values 50-60 nM)...
April 5, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29617443/changes-in-serum-levels-of-autotaxin-with-direct-acting-antiviral-therapy-in-patients-with-chronic-hepatitis-c
#12
Tomoo Yamazaki, Satoru Joshita, Takeji Umemura, Yoko Usami, Ayumi Sugiura, Naoyuki Fujimori, Takefumi Kimura, Akihiro Matsumoto, Koji Igarashi, Masao Ota, Eiji Tanaka
Sustained virological response (SVR) rates have increased remarkably since the introduction of direct-acting antiviral agents (DAAs) for chronic hepatitis C. Autotaxin (ATX) is a secreted enzyme converting lysophosphatidylcholine to lysophosphatidic acid and a newly established biomarker for liver fibrosis. Interferon-free DAA regimens for chronic hepatitis C could improve liver stiffness in SVR patients according to several non-invasive evaluation methods, but the clinical response and significance of ATX in this context have not yet been defined...
2018: PloS One
https://www.readbyqxmd.com/read/29573844/expression-of-genes-for-enzymes-synthesizing-lysophosphatidic-acid-its-receptors-and-follicle-developmental-factors-derived-from-the-cumulus-oocyte-complex-is-dependent-on-the-ovarian-follicle-type-in-cows
#13
Emilia Sinderewicz, Katarzyna Grycmacher, Dorota Boruszewska, Ilona Kowalczyk-Zięba, Joanna Staszkiewicz-Chodor, Krzysztof Łukaszuk, Izabela Wocławek-Potocka
Cumulus-oocyte complexes (COCs) release factors potentially involved in follicular growth and development, such as growth and differentiation factor 9 (GDF9), bone-morphogenetic protein 15 (BMP15), follistatin (FST) and cathepsins (CTSs). Moreover, the quality of the oocytes and follicles may be related to both the lipid composition of the follicle cells and follicular fluid. One of the lipids, locally regulating the reproductive functions in ovaries of cattle, is lysophosphatidic acid (LPA). In this study, the expression was investigated of the genes for LPA and other factors in COCs of follicles at different stages of development and regression...
March 19, 2018: Animal Reproduction Science
https://www.readbyqxmd.com/read/29570618/lysophosphatidic-acid-signaling-in-obesity-and-insulin-resistance
#14
REVIEW
Kenneth D'Souza, Geena V Paramel, Petra C Kienesberger
Although simple in structure, lysophosphatidic acid (LPA) is a potent bioactive lipid that profoundly influences cellular signaling and function upon binding to G protein-coupled receptors (LPA1-6). The majority of circulating LPA is produced by the secreted enzyme autotaxin (ATX). Alterations in LPA signaling, in conjunction with changes in autotaxin (ATX) expression and activity, have been implicated in metabolic and inflammatory disorders including obesity, insulin resistance, and cardiovascular disease...
March 23, 2018: Nutrients
https://www.readbyqxmd.com/read/29568204/serum-autotaxin-levels-are-correlated-with-hepatic-fibrosis-and-ballooning-in-patients-with-non-alcoholic-fatty-liver-disease
#15
Naoyuki Fujimori, Takeji Umemura, Takefumi Kimura, Naoki Tanaka, Ayumi Sugiura, Tomoo Yamazaki, Satoru Joshita, Michiharu Komatsu, Yoko Usami, Kenji Sano, Koji Igarashi, Akihiro Matsumoto, Eiji Tanaka
AIM: To examine the relationship between serum autotaxin (ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled. Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays. Sera obtained from 160 healthy, non-obese individuals were used as controls...
March 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29549312/measurement-of-plasma-choline-in-acute-coronary-syndrome-importance-of-suitable-sampling-conditions-for-this-assay
#16
Ryunosuke Ohkawa, Makoto Kurano, Noboru Sakai, Tatsuya Kishimoto, Takahiro Nojiri, Koji Igarashi, Shigemi Hosogaya, Yukio Ozaki, Tomotaka Dohi, Katsumi Miyauchi, Hiroyuki Daida, Junken Aoki, Shigeo Okubo, Hitoshi Ikeda, Minoru Tozuka, Yutaka Yatomi
Blood choline has been proposed as a predictor of acute coronary syndrome (ACS), however different testing procedures might affect the choline concentration because the lysophospholipase D activity of autotaxin (ATX) can convert lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline in human blood. Although the influences of ATX on LPA levels are well known in vivo and in vitro, those on choline have not been elucidated. Therefore, we established suitable sampling conditions and evaluated the usefulness of plasma choline concentrations as a biomarker for ACS...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29543710/coming-of-age-for-autotaxin-and-lysophosphatidate-signaling-clinical-applications-for-preventing-detecting-and-targeting-tumor-promoting-inflammation
#17
REVIEW
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
https://www.readbyqxmd.com/read/29500864/association-between-serum-autotaxin-or-phosphatidylserine-specific-phospholipase-a1-levels-and-melanoma
#18
Makoto Kurano, Tomomitsu Miyagaki, Takuya Miyagawa, Koji Igarashi, Satoshi Shimamoto, Hitoshi Ikeda, Junken Aoki, Shinichi Sato, Yutaka Yatomi
Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA1 ) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA1 levels and melanoma...
May 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29477073/discovery-and-optimization-of-atx-inhibitors-via-modeling-synthesis-and-biological-evaluation
#19
Anand Balupuri, Myeong Hwi Lee, Sangeun Chae, Eunmi Jung, Woosub Yoon, Yunki Kim, So Jung Son, Jeonghee Ryu, Dae-Hyuck Kang, Young-Jae Yang, Ji-Na You, Hyunjin Kwon, Jong-Woo Jeong, Tae-Sung Koo, Dae-Yon Lee, Nam Sook Kang
Autotaxin (ATX) is a potential target for the treatment of various cancers. A new series of ATX inhibitors was rationally designed and synthesized based on our previous study. Biological evaluation and structure-activity relationship (SAR) of this series are discussed. Among fourteen synthesized derivatives, six compounds (2, 3, 4, 12, 13 and 14) exhibited enhanced ATX inhibitory activities with IC50 values in the low nanomolar range. Molecular interactions of all the synthesized compounds within the active site of ATX were studied through molecular docking studies...
March 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29457888/potential-therapeutic-applications-for-inhibitors-of-autotaxin-a-bioactive-lipid-producing-lysophospholipase-d-in-disorders-affecting-the-nervous-system
#20
Deron R Herr, Jolin Hwee-Jing Ong, Wei-Yi Ong
Autotaxin is a dual-function ecto-enzyme, encoded by the gene ENPP2, which is the primary source of the bioactive signaling lipid, lysophosphatidic acid. Aberrations in autotaxin/lysophosphatidic acid signaling have been associated with a number of neurological, psychiatric, neoplastic, and neurodevelopmental conditions, such as pain, pruritus, glioblastoma multiforme, multiple sclerosis, Alzheimer's disease, hydrocephalus, and schizophrenia. This Viewpoint offers a brief overview of the likely indications for therapeutic targeting of autotaxin, in disorders affecting the nervous system...
March 21, 2018: ACS Chemical Neuroscience
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