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https://www.readbyqxmd.com/read/28792932/structural-insights-into-ligand-recognition-by-the-lysophosphatidic-acid-receptor-lpa6
#1
Reiya Taniguchi, Asuka Inoue, Misa Sayama, Akiharu Uwamizu, Keitaro Yamashita, Kunio Hirata, Masahito Yoshida, Yoshiki Tanaka, Hideaki E Kato, Yoshiko Nakada-Nakura, Yuko Otani, Tomohiro Nishizawa, Takayuki Doi, Tomohiko Ohwada, Ryuichiro Ishitani, Junken Aoki, Osamu Nureki
Lysophosphatidic acid (LPA) is a bioactive lipid composed of a phosphate group, a glycerol backbone, and a single acyl chain that varies in length and saturation. LPA activates six class A G-protein-coupled receptors to provoke various cellular reactions. Because LPA signalling has been implicated in cancer and fibrosis, the LPA receptors are regarded as promising drug targets. The six LPA receptors are subdivided into the endothelial differentiation gene (EDG) family (LPA1-LPA3) and the phylogenetically distant non-EDG family (LPA4-LPA6)...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28770493/measurement-of-lysophosphatidic-acid-and-sphingosine-1-phosphate-by-liquid-chromatography-coupled-electrospray-ionization-tandem-mass-spectrometry
#2
Maria P Kraemer, Suchismita Halder, Susan S Smyth, Andrew J Morris
Lysophosphatidic acids and sphingosine-1-phosphate are bioactive lipids that regulate diverse cellular and physiological processes through actions that are largely mediated by cell surface receptors. The roles played by these lipids in multiple disease processes make the enzymes and receptors involved in their synthesis, inactivation, and signaling attractive targets for pharmacological therapies. In this chapter we describe methods for sensitive accurate quantitation of LPA and S1P levels in biological fluids using liquid chromatography-coupled electrospray ionization tandem mass spectrometry...
August 3, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28766061/lysophosphatidic-acid-enhances-human-umbilical-cord-mesenchymal-stem-cell-viability-without-differentiation-via-lpa-receptor-mediating-manner
#3
Narengerile Li, Ya-Li Yan, Sachaofu Fu, Rui-Juan Li, Peng-Fei Zhao, Xi-Yuan Xu, Jing-Ping Yang, Alatangaole Damirin
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy...
August 1, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28765952/mtor-signaling-promotes-foam-cell-formation-and-inhibits-foam-cell-egress-through-suppressing-the-sirt1-signaling-pathway
#4
Haixiang Zheng, Yucai Fu, Yusheng Huang, Xinde Zheng, Wei Yu, Wei Wang
Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765047/lysophosphatidic-acid-individually-induces-macrophage-derived-foam-cell-formation-by-blocking-the-expression-of-srbi
#5
Linmu Chen, Jun Zhang, Xiao Deng, Yan Liu, Xi Yang, Qiong Wu, Chao Yu
The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells...
July 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28739650/lysophosphatidic-acid-receptor-antagonism-protects-against-diabetic-nephropathy-in-a-type-2-diabetic-model
#6
Ming-Zhi Zhang, Xin Wang, Haichun Yang, Agnes B Fogo, Brian J Murphy, Robert Kaltenbach, Peter Cheng, Bradley Zinker, Raymond C Harris
Lysophosphatidic acid (LPA) functions through activation of LPA receptors (LPARs). LPA-LPAR signaling has been implicated in development of fibrosis. However, the role of LPA-LPAR signaling in development of diabetic nephropathy (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of age led to a significant reduction in albuminuria, similar to that observed with renin-angiotensin system inhibition (losartan plus enalapril)...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28735625/free-fatty-acid-receptor-ffar-agonists-inhibit-proliferation-of-human-ovarian-cancer-cells
#7
Mandi M Hopkins, Kathryn E Meier
Many cellular actions of omega-3 fatty acids are mediated by two G protein-coupled receptors, FFA1 and FFA4, free fatty acid receptor (FFAR) family members that are activated by these dietary constituents. FFAR agonists inhibit proliferation of human prostate and breast cancer cells. Since omega-3 fatty acids can inhibit ovarian cancer cell growth, the current study tested the potential role of FFARs in the response. OVCAR3 and SKOV3 human ovarian cancer cell lines express mRNA for FFA1; FFA4 mRNA was detected at low levels in SKOV3 but not OVCAR3...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28716732/lysophosphatidic-acid-signaling-regulates-the-klf9-ppar%C3%AE-axis-in-human-induced-pluripotent-stem-cell-derived-neurons
#8
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
#9
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
#10
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
#11
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
#12
Román D Moreno-Fernández, Sara Tabbai, Estela Castilla-Ortega, Margarita Pérez-Martín, Guillermo Estivill-Torrús, Fernando Rodríguez de Fonseca, Luis J Santín, Carmen Pedraza
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
#13
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
#14
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
#15
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
#16
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
#17
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 16, 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
#18
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
#19
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
#20
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
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