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https://www.readbyqxmd.com/read/28716732/lysophosphatidic-acid-signaling-regulates-the-klf9-ppar%C3%AE-axis-in-human-induced-pluripotent-stem-cell-derived-neurons
#1
Tamotsu Tsukahara, Shuhei Yamagishi, Yoshikazu Matsuda, Hisao Haniu
Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated nuclear receptor, as well as its cognate receptor LPA1 on human iPSC-derived neurons to enhance proliferation and neurite outgrowth...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708504/study-of-lysophosphatidic-acid-receptors-lpars-in-buffalo-uterus-demonstrated-upregulation-of-lpar1-and-lpar6-in-early-pregnancy
#2
Abdul Sadam, Subhashree Parida, Amol R Padol, Ankita D Verma, Naseer Ahmad Baba, Wanta M Khuman, Vivek Srivastava, Manjit Panigrahi, Thakur Uttam Singh, Souvendra Nath Sarkar
Lysophosphatidic acid (LPA) is an important factor involved in embryo implantation and pregnancy establishment in humans and domestic livestock. LPA exerts its action through six G-protein-coupled receptors (LPA1-LPA6). We investigated the types of LPA receptors expressed in buffalo uterus and also their differential expression in the nonpregnant, and early-pregnant endometrium. The nonpregnant, and early-pregnant (<42 days) uteri were collected from the local slaughterhouse. RT-PCR experiments detected mRNAs of all the six LPA receptors (LPAR1-LPAR6) in both nonpregnant, and early-pregnant endometrial tissues...
May 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/28705936/cd14-is-a-key-mediator-of-both-lysophosphatidic-acid-and-lipopolysaccharide-induction-of-foam-cell-formation
#3
Dong An, Feng Hao, Fuqiang Zhang, Wei Kong, Jerold Chun, Xuemin Xu, Mei-Zhen Cui
Macrophage uptake of oxidized lowdensity lipoprotein (oxLDL) plays an important role in foam cell formation and the pathogenesis of atherosclerosis. We report here that lysophosphatidic acid (LPA) enhances lipopolysaccharide (LPS)-induced oxLDL uptake in macrophages. Our data revealed that both LPA and LPS highly induce the CD14 expression at messenger RNA and protein levels in macrophages. The role of CD14, one component of the LPS receptor cluster, in LPA-induced biological functions has been unknown. We took several steps to examine the role of CD14 in LPA signaling pathways...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28703125/flat-clathrin-lattices-are-dynamic-actin-controlled-hubs-for-clathrin-mediated-endocytosis-and-signalling-of-specific-receptors
#4
Daniela Leyton-Puig, Tadamoto Isogai, Elisabetta Argenzio, Bram van den Broek, Jeffrey Klarenbeek, Hans Janssen, Kees Jalink, Metello Innocenti
Clathrin lattices at the plasma membrane coat both invaginated and flat regions forming clathrin-coated pits and clathrin plaques, respectively. The function and regulation of clathrin-coated pits in endocytosis are well understood but clathrin plaques remain enigmatic nanodomains. Here we use super-resolution microscopy, molecular genetics and cell biology to show that clathrin plaques contain the machinery for clathrin-mediated endocytosis and cell adhesion, and associate with both clathrin-coated pits and filamentous actin...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28699486/stress-depression-resilience-and-ageing-a-role-for-the-lpa-lpa1-pathway
#5
Moreno-Fernández Román D, Tabbai Sara, Castilla-Ortega Estela, Pérez-Martín Margarita, Estivill-Torrús Guillermo, Rodríguez de Fonseca Fernando, Santín Luis J, Pedraza Carmen
BACKGROUND: Chronic stress affects health and the quality of life, with its effects being particularly relevant in ageing due to the psychobiological characteristics of this population. However, while some people develop psychiatric disorders, especially depression, others seem very capable of dealing with adversity. There is no doubt that along with the identification of neurobiological mechanisms involved in developing depression, discovering which factors are involved in positive adaptation under circumstances of extreme difficulty will be crucial for promoting resilience...
July 10, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28674249/effects-of-gintonin-enriched-fraction-in-an-atopic-dermatitis-animal-model-involvement-of-autotaxin-regulation
#6
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
#7
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/28657680/lysophosphatidic-acid-triggered-pathways-promote-the-acquisition-of-trophoblast-endovascular-phenotype-in-vitro
#8
Jimena S Beltrame, Micaela S Sordelli, Vanesa A Cañumil, Ana M Franchi, María L Ribeiro
Successful implantation and placentation requires that extravillous cytotrophoblast acquires an endovascular phenotype and remodels uterine spiral arteries. Defects in this mechanism correlate with severe obstetric complications as implantation failure and preeclampsia. Lysophosphatidic acid (LPA) participates in embryo implantation and contributes to vascular physiology in different biological systems. However, the role of LPA on trophoblast endovascular transformation has not been studied. Due to difficulties in studying human pregnancy in vivo, we adopted a pharmacological approach in vitro to investigate LPA action in various aspects of trophoblast endovascular response, such as the formation of endothelial capillary-like structures, migration and proliferation...
June 28, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28611684/protective-role-for-lpa3-in-cardiac-hypertrophy-induced-by-myocardial-infarction-but-not-by-isoproterenol
#9
Lin Cai, Guangpu Fan, Fang Wang, Si Liu, Tiewei Li, Xiangfeng Cong, Jerold Chun, Xi Chen
Background: We previously reported that lysophosphatidic acid (LPA) promoted cardiomyocyte hypertrophy in vitro via one of its G protein-coupled receptor subtypes, LPA3. In this study, we examined the role of LPA3 in cardiac hypertrophy induced by isoproterenol (ISO) and myocardial infarction. Methods:In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to LPA3 knocked-down, or pretreated with a β-adrenergic receptor (β-AR) antagonist (propranolol) before LPA/ISO treatment. Cardiomyocyte size and hypertrophic gene (ANP, BNP) mRNA levels were determined...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28595938/bifidobacteria-derived-lipoproteins-inhibit-infection-with-coxsackievirus-b4-in-vitro
#10
Khalil Antoine El Kfoury, Marie-Bénédicte Romond, Angelo Scuotto, Enagnon Kazali Alidjinou, Fouad Dabboussi, Monzer Hamze, Ilka Engelmann, Famara Sane, Didier Hober
The aim of the present study was to investigate the potential of bifidobacteria in protecting cells from coxsackievirus B4 (CV-B4) infection. Bifidobacterial screening identified two of five strains that protected human epithelial type 2 (HEp-2) cell viability when bifidobacteria were incubated with viral particles prior to inoculation. In contrast, no effect was shown by incubating HEp-2 cells with bifidobacteria prior to CV-B4 inoculation. Cell wall lipoprotein aggregates (LpAs) secreted by the selected strains were assayed for their antiviral activity...
June 5, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28588064/autotaxin-lysophosphatidic-acid-lpa3-signaling-at-the-embryo-epithelial-boundary-controls-decidualization-pathways
#11
Shizu Aikawa, Kuniyuki Kano, Asuka Inoue, Jiao Wang, Daisuke Saigusa, Takeshi Nagamatsu, Yasushi Hirota, Tomoyuki Fujii, Soken Tsuchiya, Yoshitaka Taketomi, Yukihiko Sugimoto, Makoto Murakami, Makoto Arita, Makoto Kurano, Hitoshi Ikeda, Yutaka Yatomi, Jerold Chun, Junken Aoki
During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA3 in the uterine epithelium. Knockout of Lpar3 or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions...
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28554198/role-of-taz-in-lysophosphatidic-acid-induced-migration-and-proliferation-of-human-adipose-derived-mesenchymal-stem-cells
#12
Won Min Mo, Yang Woo Kwon, Il Ho Jang, Eun Jung Choi, Sang Mo Kwon, Jae Ho Kim
Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs...
July 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28539367/implications-for-breast-cancer-treatment-from-increased-autotaxin-production-in-adipose-tissue-after-radiotherapy
#13
Guanmin Meng, Xiaoyun Tang, Zelei Yang, Matthew G K Benesch, Alison Marshall, David Murray, Denise G Hemmings, Frank Wuest, Todd P W McMullen, David N Brindley
We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy...
May 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28512139/a-genome-wide-association-meta-analysis-on-lipoprotein-a-concentrations-adjusted-for-apolipoprotein-a-isoforms
#14
Salome Mack, Stefan Coassin, Rico Rueedi, Noha A Yousri, Ilkka Seppälä, Christian Gieger, Sebastian Schönherr, Lukas Forer, Gertraud Erhart, Pedro Marques-Vidal, Janina Ried, Gerard Waeber, Sven Bergmann, Doreen Dähnhardt, Andrea Stöckl, Olli T Raitakari, Mika Kähönen, Annette Peters, Thomas Meitinger, Konstantin Strauch, Ludmilla Kedenko, Bernhard Paulweber, Terho Lehtimäki, Steven C Hunt, Peter Vollenweider, Claudia Lamina, Florian Kronenberg
High lipoprotein(a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) KIV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n=13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region)...
May 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#15
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28496416/lysophosphatidic-acid-is-associated-with-atherosclerotic-plaque-instability-by-regulating-nf-%C3%AE%C2%BAb-dependent-matrix-metalloproteinase-9-expression-via-lpa2-in-macrophages
#16
Chun Gu, Fang Wang, Zhenwen Zhao, Hongyue Wang, Xiangfeng Cong, Xi Chen
Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM) degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28472283/oxldl-derived-lysophosphatidic-acid-promotes-the-progression-of-aortic-valve-stenosis-through-a-lpar1-rhoa-nf-%C3%AE%C2%BAb-pathway
#17
Mohamed Jalloul Nsaibia, Marie-Chloé Boulanger, Rihab Bouchareb, Ghada Mkannez, Khai Le Quang, Fayez Hadji, Deborah Argaud, Abdellaziz Dahou, Yohan Bossé, Marlys L Koschinsky, Philippe Pibarot, Benoit J Arsenault, André Marette, Patrick Mathieu
AIMS: Oxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least 6 different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28460684/effects-of-lpa2r-lpa3r-or-ep4r-agonists-on-luteal-or-endometrial-function-in%C3%A2-vivo-or-in%C3%A2-vitro-and-sirtuin-or-ep1r-ep2r-ep3r-or-ep4r-agonists-on-endometrial-secretion-of-pge-and-pgf2%C3%AE-in%C3%A2-vitro
#18
Magen E LaPorte, Yoshie S Weems, Alejandro Arreguin-Arevalo, Terry M Nett, Nicole Tsutahara, Tracy Sy, Jade Haberman, Michel Chon, Ronald D Randel, Charles W Weems
In previous work, an EP2 prostanoid receptor (EP2R) agonist in vivo increased mRNA expression of luteal LH receptors (LHR), unoccupied and occupied luteal; LHR, and circulating progesterone, while an EP3R or FPR agonist decreased; mRNA expression of luteal LHR, unoccupied and occupied luteal LHR, and; circulating progesterone. An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have been proposed to increase prostaglandin synthesis. The objectives were to determine; whether an EP4R, LPA2R, or LPA3R agonist affect ovine luteal function in vivo or; in vitro...
June 2017: Theriogenology
https://www.readbyqxmd.com/read/28460477/inhibition-of-lysophosphatidic-acid-receptor-ameliorates-sj%C3%A3-gren-s-syndrome-in-nod-mice
#19
Eunhye Park, Donghee Kim, Song Mi Lee, Hee-Sook Jun
Lysophosphatidic acid (LPA), a bioactive lysophospholipid, is involved in the pathogenesis of chronic inflammatory and autoimmune diseases. In this study, we investigated the role of LPA/LPA receptor (LPAR) signaling in the pathogenesis of Sjögren's syndrome (SS). We found that autotaxin, an LPA producing enzyme, and LPAR1 and LPAR3 mRNA, and IL-17 mRNA were highly expressed in the exocrine glands of 20-week-old nonobese diabetic (NOD) mice, which show SS symptoms at this age, as compared with non-symptomatic 8-week-old NOD mice...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447863/lysophosphatidic-acid-and-amitriptyline-signal-through-lpa1r-to-reduce-p-glycoprotein-transport-at-the-blood-brain-barrier
#20
David B Banks, Gary Ny Chan, Rebecca A Evans, David S Miller, Ronald E Cannon
The blood-brain barrier is a microvascular network that (1) provides neuroprotection from metabolic and environmental toxins and (2) limits the delivery of therapeutics to the central nervous system (CNS). The ATP-binding cassette transporter P-glycoprotein contributes to the latter by actively pumping clinical substrates back into circulation before they can reach the brain parenchyma. Targeting P-glycoprotein has proven effective in increasing the delivery of therapeutics to their cerebral targets. We provide a novel mechanism to achieve this end in functioning, intact rat brain capillaries, whereby the bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that requires G-protein coupling, Src kinase, and ERK 1/2...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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