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https://www.readbyqxmd.com/read/28512139/a-genome-wide-association-meta-analysis-on-lipoprotein-a-concentrations-adjusted-for-apolipoprotein-a-isoforms
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28432900/lysophosphatidic-acid-induces-expression-of-genes-in-human-oral-keratinocytes-involved-in-wound-healing
#8
Hong Huynh Thorlakson, Stian Andre Engen, Olav Schreurs, Karl Schenck, Inger Johanne Schytte Blix
OBJECTIVE: Epithelial cells participate in wound healing by covering wounds, but also as important mediators of wound healing processes. Topical application of the phospholipid growth factor lysophosphatidic acid (LPA) accelerates dermal wound healing and we hypothesized that LPA can play a role in human oral wound healing through its effects on human oral keratinocytes (HOK). DESIGN: HOK were isolated from gingival biopsies and exposed to LPA. The LPA receptor profile, signal transduction pathways, gene expression and secretion of selected cytokines were analyzed...
April 13, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28392399/preparation-of-functional-human-lysophosphatidic-acid-receptor-2-using-a-p9-%C3%A2-expression-system-and-an-amphipathic-polymer-and-investigation-of-its-in%C3%A2-vitro-binding-preference-to-g%C3%AE-proteins
#9
Seong-Gu Han, Seung-Il Baek, Tae Jin Son, Hyeongjin Lee, Nam Hyuk Kim, Yeon Gyu Yu
Human lysophosphatidic acid receptor 2 (LPA2), a member of the G-protein coupled receptor family, mediates lysophosphatidic acid (LPA)-dependent signaling by recruiting various G proteins. Particularly, it is directly implicated in the progression of colorectal and ovarian cancer through G protein signaling cascades. To investigate the biochemical binding properties of LPA2 against various alpha subunits of G protein (Gα), a functional recombinant LPA2 was overexpressed in E. coli membrane with a P9(∗) expression system, and the purified protein was stabilized with an amphipathic polymer that had been synthesized by coupling octylamine, glucosamine, and diethyl aminoproylamine at the carboxylic groups of poly-γ-glutamic acid...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28382003/adult-lysophosphatidic-acid-receptor-1-deficient-rats-with-hyperoxia-induced-neonatal-chronic-lung-disease-are-protected-against-lipopolysaccharide-induced-acute-lung-injury
#10
Xueyu Chen, Frans J Walther, El H Laghmani, Annemarie M Hoogeboom, Anne C B Hogen-Esch, Ingrid van Ark, Gert Folkerts, Gerry T M Wagenaar
Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28377726/lysophosphatidic-acid-pretreatment-attenuates-myocardial-ischemia-reperfusion-injury-in-the-immature-hearts-of-rats
#11
Haibo Chen, Si Liu, Xuewen Liu, Jinjing Yang, Fang Wang, Xiangfeng Cong, Xi Chen
The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1-LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28376314/endogenous-lysophosphatidic-acid-participates-in-vascularisation-and-decidualisation-at-the-maternal-fetal-interface-in-the-rat
#12
Micaela S Sordelli, Jimena S Beltrame, Elsa Zotta, Natalia Gomez, Ganna Dmytrenko, María Elena Sales, Sandra M Blois, Carlos Davio, Silvina Perez Martinez, Ana M Franchi, María L Ribeiro
Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA3 receptors, on Day 5 of gestation...
April 5, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28359316/evaluation-of-pancreatic-cancer-cell-migration-with-multiple-parameters-in-vitro-by-using-an-optical-real-time-cell-mobility-assay-device
#13
Akira Yamauchi, Masahiro Yamamura, Naoki Katase, Masumi Itadani, Naoko Okada, Kayoko Kobiki, Masafumi Nakamura, Yoshiyuki Yamaguchi, Futoshi Kuribayashi
BACKGROUND: Migration of cancer cell correlates with distant metastasis and local invasion, which are good targets for cancer treatment. An optically accessible device "TAXIScan" was developed, which provides considerably more information regarding the cellular dynamics and less quantity of samples than do the existing methods. Here, we report the establishment of a system to analyze the nature of pancreatic cancer cells using TAXIScan and we evaluated lysophosphatidic acid (LPA)-elicited pancreatic cell migration...
March 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28348461/am966-an-antagonist-of-lysophosphatidic-acid-receptor-1-increases-lung-microvascular-endothelial-permeability-through-activation-of-rho-signaling-pathway-and-phosphorylation-of-ve-cadherin
#14
Junting Cai, Jianxin Wei, Shuang Li, Tomeka Suber, Jing Zhao
Maintenance of pulmonary endothelial barrier integrity is important for reducing severity of lung injury. Lysophosphatidic acid (LPA) regulates cell motility, cytoskeletal rearrangement, and cell growth. Knockdown of LPA receptor 1 (LPA1) has been shown to mitigate lung injury and pulmonary fibrosis. AM966, an LPA1 antagonist exhibiting an antifibrotic property, has been considered to be a future antifibrotic medicine. Here, we report an unexpected effect of AM966, which increases lung endothelial barrier permeability...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28348459/lysophosphatidic-acid-triggers-apoptosis-in-hela-cells-through-the-upregulation-of-tumor-necrosis-factor-receptor-superfamily-member-21
#15
Yunzhou Dong, Yong Wu, Mei-Zhen Cui, Xuemin Xu
Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid, activates G protein-coupled receptors (GPCRs), leading to regulation of diverse cellular events including cell survival and apoptosis. Despite extensive studies of the signaling pathways that mediate LPA-regulated cell growth and survival, the mechanisms underlying the apoptotic effect of LPA remain largely unclear. In this study, we investigated this issue in HeLa cells. Our data demonstrate that LPA induces apoptosis in HeLa cells at pathologic concentrations with a concomitant upregulation of the expression of TNFRSF21 (tumor necrosis factor receptor superfamily member 21), also known as death receptor number 6 (DR6) involved in inflammation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28346103/discovery-of-novel-gq-biased-lpa1-negative-allosteric-modulators
#16
Yuji Shimizu, Masaharu Nakayama
Lysophosphatidic acid (LPA) activates the G-protein-coupled receptor LPA1, which regulates various cellular processes, including cell proliferation and migration. Although LPA1 transduces cellular responses via Gq, Gi, and G12/13, associations between these signaling molecules and cellular phenotypes remain poorly characterized due to the lack of signal-specific pharmacological tools. Here, we characterized novel signal-biased modulators using multiple assays, including label-free impedance assays. LPA caused dramatic changes in cellular impedance in LPA1-expressing recombinant cells, which were susceptible to G-protein and protein kinase inhibitors...
February 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28342860/functional-characterization-of-lysophosphatidic-acid-receptor-1-mutants-identified-in-rat-cancer-tissues
#17
Shoichi Ishii, Toshifumi Tsujiuchi, Nobuyuki Fukushima
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28324037/autotaxin-is-regulated-by-glucose-and-insulin-in-adipocytes
#18
Kenneth D'Souza, Daniel A Kane, Mohamed Touaibia, Erin E Kershaw, Thomas Pulinilkunnil, Petra C Kienesberger
Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The current study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas coincubation with the insulin sensitizer, rosiglitazone, prevented this response...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323698/hypertrophy-and-fibrosis-of-the-ligamentum-flavum-in-lumbar-spinal-stenosis-is-associated-with-increased-expression-of-lpa-and-lpar1
#19
Kai Zhang, Wei Sun, Xin-Yu Liu, Chang-Qing Zhao, Hua Li, Xiao-Jiang Sun, Xie You-Zhuan, Wei Ding, Jie Zhao
STUDY DESIGN: Histologic, immunohistochemical (IHC), and enzyme-linked immunosorbent assay analysis of the human ligamentum flavum (LF). OBJECTIVE: The purpose of this study was to determine the level of expression of lysophosphatidic acid (LPA) in the LF from lumbar spinal stenosis (LSS) patients and to analyze the relationship among LPA, LPA receptors (LPARs), and LF hypertrophy. SUMMARY OF BACKGROUND DATA: LF hypertrophy and fibrosis are important causes of LSS...
April 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28314177/gintonin-attenuates-depressive-like-behaviors-associated-with-alcohol-withdrawal-in-mice
#20
Hyeon-Joong Kim, Sang-Deuk Park, Ra Mi Lee, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Panax ginseng Meyer extracts have been used to improve mood and alleviate symptoms of depression. However, little is known about the extracts' active ingredients and the molecular mechanisms underlying their reported anti-depressive effects. METHODS: Gintonin is an exogenous lysophosphatidic acid (LPA) receptor ligand isolated from P. ginseng. BON cells, an enterochromaffin cell line, and C57BL/6 mice were used to investigate whether gintonin stimulates serotonin release...
March 9, 2017: Journal of Affective Disorders
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