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Lysophosphatidic acid

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https://www.readbyqxmd.com/read/28073697/proliferation-of-mouse-endometrial-stromal-cells-in-culture-is-highly-sensitive-to-lysophosphatidic-acid-signaling
#1
Shizu Aikawa, Kuniyuki Kano, Asuka Inoue, Naoto Hama, Yoshiharu Iwabuchi, Junken Aoki
Endometrial stromal cells (ESCs) proliferate rapidly both in vivo and in vitro. Here we show that proliferation of ESCs in vitro is strongly dependent on lysophosphatidic acid (LPA) signaling. LPA is produced by autotaxin (ATX) and induces various kinds of cellular processes including migration, proliferation and inhibition of cell death possibly through six G protein-coupled receptors (LPA1-6). We found that ESCs proliferated rapidly in vitro in an autocrine manner and that the proliferation was prominently suppressed by either an ATX inhibitor (ONO-8430506) or an LPA1/3 antagonist (Ki16425)...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#2
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069607/lysophosphatidic-acid-converts-monocytes-into-macrophages-in-both-mice-and-humans
#3
Rashmi Ray, Vivek Rai
Monocytes and macrophages represent critical arms of the innate immune system and are considered regulators and effectors of inflammation and innate immune response. Monocytes can mobilize from bone marrow, traffic to their required destination and differentiate into effector cells depending on the local tissue environment to perform multiple roles during infection or inflammation, making them an important component of body's immune defense. Macrophages have diverse roles in tissue homeostasis, development as well as tissue repair following injury...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28052132/association-between-promoter-hypomethylation-and-overexpression-of-autotaxin-with-outcome-parameters-in-biliary-atresia
#4
Wanvisa Udomsinprasert, Nakarin Kitkumthorn, Apiwat Mutirangura, Voranush Chongsrisawat, Yong Poovorawan, Sittisak Honsawek
OBJECTIVE: Biliary atresia (BA) is a progressive fibroinflammatory liver disease. Autotaxin (ATX) has a profibrotic effect resulting from lysophosphatidic acid activity. The purpose of this study was to examine ATX expression and ATX promoter methylation in peripheral blood leukocytes and liver tissues from BA patients and controls and investigate their associations with outcome parameters in BA patients. METHODS: A total of 130 subjects (65 BA patients and 65 age-matched controls) were enrolled...
2017: PloS One
https://www.readbyqxmd.com/read/28050783/daily-intake-of-high-fat-diet-with-lysophosphatidic-acid-rich-soybean-phospholipids-augments-colon-tumorigenesis-in-kyoto-apc-delta-rats
#5
Toshihiko Tsutsumi, Manami Inoue, Yoko Okamoto, Akira Ishihara, Akira Tokumura
BACKGROUND: Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice. AIMS: The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats. METHODS: Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis...
January 3, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28035350/silencing-lpaat%C3%AE-inhibits-tumor-growth-of-cisplatin-resistant-human-osteosarcoma-in-vivo-and-in-vitro
#6
Lei Song, Ping Duan, Yibo Gan, Pei Li, Chen Zhao, Jianzhong Xu, Zehua Zhang, Qiang Zhou
Cisplatin-resistance has become a major impediment in the medical treatment of cancers such as osteosarcoma, the most common primary malignancy of bone. Since lysophosphatidic acid acyltransferase β (LPAATβ) was reported to be critically involved in osteosarcoma, our study investigated the role of LPAATβ in human osteosarcoma with cisplatin-resistance. Expression of LPAATβ or other relevant proteins were analyzed in 40 osteosarcoma patients by immunohistochemistry analysis (IHC), and in cisplatin‑resistant sublines by real-time PCR and western blotting...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28028754/alteration-of-lysophosphatidylcholine-related-metabolic-parameters-in-the-plasma-of-mice-with-experimental-sepsis
#7
Won-Gyun Ahn, Jun-Sub Jung, Hyeok Yil Kwon, Dong-Keun Song
Plasma concentration of lysophosphatidylcholine (LPC) was reported to decrease in patients with sepsis. However, the mechanisms of sepsis-induced decrease in plasma LPC levels are not currently well known. In mice subjected to cecal ligation and puncture (CLP), a model of polymicrobial peritoneal sepsis, we examined alterations in LPC-related metabolic parameters in plasma, i.e., the plasma concentration of LPC-related substances (i.e., phosphatidylcholine (PC) and lysophosphatidic acid (LPA)), and activities or levels in the plasma of some enzymes that can be involved in the regulation of plasma LPC concentration (i...
December 28, 2016: Inflammation
https://www.readbyqxmd.com/read/28007846/different-origins-of-lysophospholipid-mediators-between-coronary-and-peripheral-arteries-in-acute-coronary-syndrome
#8
Makoto Kurano, Kuniyuki Kano, Tomotaka Dohi, Hirotaka Matsumoto, Koji Igarashi, Masako Nishikawa, Ryunosuke Ohkawa, Hitoshi Ikeda, Katsumi Miyauchi, Hiroyuki Daida, Junken Aoki, Yutaka Yatomi
Lysophosphatidic acids (LysoPA) and lysophosphatidylserine (LysoPS) are emerging lipid mediators proposed to be involved in the pathogenesis of acute coronary syndrome (ACS). In this study, we attempted to elucidate how LysoPA and LysoPS become elevated in ACS using human blood samples collected simultaneously from culprit coronary arteries and peripheral arteries in ACS subjects. We found that (1) the plasma LysoPA, LysoPS, and lysophosphatidylglycerol levels were not different, while the lysophosphatidylcholine (LysoPC), lysophosphatidylinositol, and lysophosphatidylethanolamine (LysoPE) levels were significantly lower in the culprit coronary arteries; (2) the serum ATX level was lower and the serum PS-PLA1 level was higher in the culprit coronary arteries; (3) the LysoPE and ATX levels were significant explanatory factors for the mainly elevated species of LysoPA, except for 22:6 LysoPA, in the peripheral arteries, while the LysoPC and LysoPE levels, but not the ATX level, were explanatory factors in the culprit coronary arteries; and (4) 18:0 and 18:1 LysoPS were significantly correlated with PS-PLA1 only in the culprit coronary arteries...
December 22, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27993681/lysophosphatidic-acid-lpa-signaling-via-lpa4-and-lpa6-negatively-regulates-cell-motile-activities-of-colon-cancer-cells
#9
Kaede Takahashi, Kaori Fukushima, Yuka Onishi, Karin Inui, Yusuke Node, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27987185/cloning-characterization-and-expression-analysis-of-a-gene-encoding-a-putative-lysophosphatidic-acid-acyltransferase-from-seeds-of-paeonia-rockii
#10
Qing-Yu Zhang, Li-Xin Niu, Rui Yu, Xiao-Xiao Zhang, Zhang-Zhen Bai, Ke Duan, Qing-Hua Gao, Yan-Long Zhang
Tree peony (Paeonia section Moutan DC.) is an excellent woody oil crop, and the cloning and functional analysis of genes related to fatty acid (FA) metabolism from this organism has not been reported. Lysophosphatidic acid acyltransferase (LPAAT), which converts lysophosphatidic acid (LPA) to phosphatidic acid (PA), catalyzes the addition of fatty acyl moieties to the sn-2 position of the LPA glycerol backbone in triacylglycerol (TAG) biosynthesis. This project reports a putative lysophosphatidic acid acyltransferase gene PrLPAAT1 isolated from Paeonia rockii...
December 16, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27982588/structure-activity-relationships-of-small-molecule-autotaxin-inhibitors-with-a-discrete-binding-mode
#11
Lisa M Miller, Willem-Jan Keune, Diana Castagna, Louise C Young, Emma L Duffy, Frances Potjewyd, Fernando Salgado-Polo, Paloma Engel García, Dima Semaan, John M Pritchard, Anastassis Perrakis, Simon J F Macdonald, Craig Jamieson, Allan J B Watson
Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signaling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, among others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold...
January 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27981605/hepatocyte-autotaxin-expression-promotes-liver-fibrosis-and-cancer
#12
Eleanna Kaffe, Aggeliki Katsifa, Nikos Xylourgidis, Ioanna Ninou, Markella Zannikou, Vaggelis Harokopos, Pelagia Foka, Alexios Dimitriadis, Kostas Evangelou, Anargyros N Moulas, Urania Georgopoulou, Vassilis G Gorgoulis, George N Dalekos, Vassilis Aidinis
: Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the production of lysophosphatidic acid (LPA), a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver diseases (CLDs) patients of different etiologies, associated with shorter overall survival...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27960085/molecular-liver-cancer-prevention-in-cirrhosis-by-organ-transcriptome-analysis-and-lysophosphatidic-acid-pathway-inhibition
#13
Shigeki Nakagawa, Lan Wei, Won Min Song, Takaaki Higashi, Sarani Ghoshal, Rosa S Kim, C Billie Bian, Suguru Yamada, Xiaochen Sun, Anu Venkatesh, Nicolas Goossens, Gretchen Bain, Gregory Y Lauwers, Anna P Koh, Mohamed El-Abtah, Noor B Ahmad, Hiroki Hoshida, Derek J Erstad, Ganesh Gunasekaran, Youngmin Lee, Ming-Lung Yu, Wan-Long Chuang, Chia-Yen Dai, Masahiro Kobayashi, Hiromitsu Kumada, Toru Beppu, Hideo Baba, Milind Mahajan, Venugopalan D Nair, Michael Lanuti, Augusto Villanueva, Angelo Sangiovanni, Massimo Iavarone, Massimo Colombo, Josep M Llovet, Aravind Subramanian, Andrew M Tager, Scott L Friedman, Thomas F Baumert, Myron E Schwarz, Raymond T Chung, Kenneth K Tanabe, Bin Zhang, Bryan C Fuchs, Yujin Hoshida
Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27927603/lysophosphatidic-acid-signaling-through-its-receptor-initiates-profibrotic-epithelial-cell-fibroblast-communication-mediated-by-epithelial-cell-derived-connective-tissue-growth-factor
#14
Norihiko Sakai, Jerold Chun, Jeremy S Duffield, David Lagares, Takashi Wada, Andrew D Luster, Andrew M Tager
The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA1-deficient (LPA1(-/-)) or -sufficient (LPA1(+/+)) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts...
December 4, 2016: Kidney International
https://www.readbyqxmd.com/read/27918822/growth-differentiation-factor-15-induced-contractile-activity-and-extracellular-matrix-production-in-human-trabecular-meshwork-cells
#15
Arumugam Ramachandran Muralidharan, Rupalatha Maddala, Nikolai P Skiba, Ponugoti Vasantha Rao
Purpose: To determine the role and regulation of growth differentiation factor-15 (GDF-15), a TGF-β-related cytokine in human trabecular meshwork (TM) cells in the context of aqueous humor (AH) outflow and IOP. Methods: Regulation of expression by external cues, and the distribution and secretion of GDF-15 by human TM primary cell cultures, and the effects of recombinant (r) GDF-15 on TM cell contractile characteristics, actin cytoskeleton, cell adhesion, extracellular matrix (ECM), α-smooth muscle actin (αSMA), SMAD signaling, and gene expression were determined by immunoblot, immunofluorescence, mass spectrometry, cDNA microarray, and real-time quantitative PCR (RT-qPCR) analyses...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27915992/plasma-phospholipids-are-associated-with-mild-cognitive-impairment-in-type-2-diabetic-patients
#16
Jin-Biao Zhang, Yan-Nan Cong, Zhen-Guang Li, Hai-Rong Sun, Jiang-Shan Zhang, Peng-Fei Wang, Qi-Zhan Wu
Phospholipids (PLs) and their metabolisms are closely allied to nosogenesis and aggravation of Type 2 diabetes mellitus and cognitive impairment. The aim of this study is to characterize the plasma levels of phospholipids in type 2 diabetes patients and type 2 diabetes patients with mild cognitive impairment (MCI), and to identify potential biomarkers of type 2 diabetes patients with MCI. In this cross-sectional study, A total of 374 type 2 diabetes patients were prospectively enrolled. There were 103 patients with MCI and 271 patients without MCI (control)...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27888146/a-rhodium-iii-based-inhibitor-of-autotaxin-with-antiproliferative-activity
#17
Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Jia-Xin Liang, Chung-Nga Ko, Jin-Jian Lu, Xiu-Ping Chen, Dik-Lung Ma, Chung-Hang Leung
BACKGROUND: Cancer of the skin is by far the most common of all cancers. Melanoma accounts for only about 1% of skin cancers but causes a large majority of skin cancer deaths. Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), regulates physiological and pathological functions of lysophosphatidic acid (LPA), and is thus an important therapeutic target. METHODS: We synthesized ten metal-based complexes and a novel cyclometalated rhodium(III) complex 1 was identified as an ATX enzymatic inhibitor using multiple methods, including ATX enzymatic assay, thermal shift assay, western immunoblotting and so on...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27885213/a-fret-biosensor-for-rock-based-on-a-consensus-substrate-sequence-identified-by-kiss-technology
#18
Chunjie Li, Ayako Imanishi, Naoki Komatsu, Kenta Terai, Mutsuki Amano, Kozo Kaibuchi, Michiyuki Matsuda
Genetically-encoded biosensors based on Förster/fluorescence resonance energy transfer (FRET) are versatile tools for studying the spatio-temporal regulation of signaling molecules within not only the cells but also tissues. Perhaps the hardest task in the development of a FRET biosensor for protein kinases is to identify the kinase-specific substrate peptide to be used in the FRET biosensor. To solve this problem, we took advantage of kinase-interacting substrate screening (KISS) technology, which deduces a consensus substrate sequence for the protein kinase of interest...
November 23, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27883058/role-of-ectonucleotide-pyrophosphatase-phosphodiesterase-2-in-the-midline-axis-formation-of-zebrafish
#19
Frisca Frisca, Daniel Colquhoun, Yona Goldshmit, Minna-Liisa Änkö, Alice Pébay, Jan Kaslin
Lysophosphatidic acid (LPA) is a unique bioactive lysophospholipid that induces pleiotropic effects in various cell types and organisms by acting on its specific receptors. LPA is mainly synthetised extracellularly by the ectonucleotide pyrophosphatase/phosphodiesterase 2/autotaxin (enpp2). Altered LPA signalling is associated with embryonic abnormalities, suggesting critical roles for LPA during development. However, the role of LPA signalling during early embryogenesis is not well established. We demonstrate that enpp2/LPA signalling in the early zebrafish embryo results in altered axis and midline formation, defects in left right (L-R) patterning, ciliogenesis of the Kupffer's vesicle (KV), through the modulation of cell migration during gastrulation in a lpar1-3 Rho/ROCK-dependant manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883026/inhibition-of-lysophosphatidic-acid-receptors-1-and-3-attenuates-atherosclerosis-development-in-ldl-receptor-deficient-mice
#20
Eva Kritikou, Gijs H M van Puijvelde, Thomas van der Heijden, Peter J van Santbrink, Maarten Swart, Frank H Schaftenaar, Mara J Kröner, Johan Kuiper, Ilze Bot
Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425...
November 24, 2016: Scientific Reports
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