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https://www.readbyqxmd.com/read/29743582/synaptic-phospholipids-as-a-new-target-for-cortical-hyperexcitability-and-e-i-balance-in-psychiatric-disorders
#1
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/29732731/double-blind-randomized-8-week-placebo-controlled-followed-by-a-16-week-open-label-extension-study-with-the-lpa1-receptor-antagonist-sar100842-for-patients-with-diffuse-cutaneous-systemic-sclerosis
#2
Yannick Allanore, Oliver Distler, Alexandre Jagerschmidt, Stephane Illiano, Laetitia Ledein, Eric Boitier, Inoncent Agueusop, Christopher P Denton, Dinesh Khanna
BACKGROUND: Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). METHODS: An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15...
May 6, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29724718/the-autotaxin-lysophosphatidic-acid-axis-promotes-lung-carcinogenesis
#3
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/29719665/effect-of-lysophosphatidic-acid-on-the-follicular-development-and-the-expression-of-lysophosphatidic-acid-receptor-genes-during-in-vitro-culture-of-mouse-ovary
#4
Neda Abedpour, Mojdeh Salehnia, Nassim Ghorbanmehr
Lysophosphatidic acid (LPA) known as a serum-derived growth factor, is involved in several cell physiological functions in the female reproductive system including: oocyte maturation, in vitro fertilization and embryo implantation by its transmembrane G protein-coupled receptors. The aim of the present study was to examine the effect of LPA on in vitro follicular development of mouse ovarian tissue. Neonatal mouse ovarian tissues were cultured in five different concentrations of LPA (0, 5, 10, 20 and 40 µM)...
2018: Veterinary Research Forum
https://www.readbyqxmd.com/read/29677358/lysophosphatidic-acid-induces-ecm-production-via-activation-of-the-mechanosensitive-yap-taz-transcriptional-pathway-in-trabecular-meshwork-cells
#5
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/29669286/platelets-promote-metastasis-via-binding-tumor-cd97-leading-to-bidirectional-signaling-that-coordinates-transendothelial-migration
#6
Yvona Ward, Ross Lake, Farhoud Faraji, Jamie Sperger, Philip Martin, Cameron Gilliard, Kimberly P Ku, Tamara Rodems, David Niles, Heather Tillman, JuanJuan Yin, Kent Hunter, Adam G Sowalsky, Joshua Lang, Kathleen Kelly
Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extracellular domain or tumor cell-associated CD97 stimulated platelet activation...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29660533/role-of-lysophosphatidic-acid-in-the-retinal-pigment-epithelium-and-photoreceptors
#7
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
#8
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/29604355/gintonin-a-ginseng-derived-exogenous-lysophosphatidic-acid-receptor-ligand-enhances-blood-brain-barrier-permeability-and-brain-delivery
#9
Do-Geun Kim, Minhee Jang, Sun-Hye Choi, Hyeon-Joong Kim, Hyunjhung Jhun, Hyoung-Chun Kim, Hyewhon Rhim, Ik-Hyun Cho, Seung-Yeol Nah
Gintonin is a ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin induces [Ca2+ ]i transient and biological effects through LPA receptor and increases the permeability of the blood-brain barrier (BBB). However, little is known about its mechanisms on the BBB. We examined the in vitro effects of gintonin using primary human brain microvascular endothelial cells (HBMECs) and the in vivo effects of gintonin on brain delivery. Fluorescent-labeled gintonin bound to HBMECs and co-localized with the LPA1 receptor...
March 28, 2018: International Journal of Biological Macromolecules
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
#10
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
#11
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/29554602/lysophosphatidic-acid-increases-in-vitro-maturation-efficiency-via-upa-upar-signaling-pathway-in-cumulus-cells
#12
Seon-Ung Hwang, Kyu-Jun Kim, Eunhye Kim, Junchul David Yoon, Kyu Mi Park, Minghui Jin, Yongquan Han, Mirae Kim, Gabsang Lee, Sang-Hwan Hyun
Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P <0...
March 2, 2018: Theriogenology
https://www.readbyqxmd.com/read/29551679/enpp2-protects-cardiomyocytes-from-erastin-induced-ferroptosis
#13
Yu-Ting Bai, Rong Chang, Hua Wang, Feng-Jun Xiao, Ri-Li Ge, Li-Sheng Wang
Ferroptosis is an iron- and oxidative-dependent form of regulated cell death and may play important roles in maintaining myocardium homeostasis and pathology of cardiovascular diseases. Currently, the regulatory roles of lipid signals in regulating cardiomyocytes ferroptosis has not been explored. In this study, we show that ENPP2, as a lipid kinase involved in lipid metabolism, protects against erastin-induced ferroptosis in cardiomyocytes. The classical ferroptosis inducer erastin remarkably inhibits the growth which could be rescued by the small molecule Fer-1 in H9c2 cells...
March 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29543710/coming-of-age-for-autotaxin-and-lysophosphatidate-signaling-clinical-applications-for-preventing-detecting-and-targeting-tumor-promoting-inflammation
#14
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/29516992/correlation-between-epidermal-growth-factor-receptor-mutation-and-histologic-subtypes-or-characteristics-of-computed-tomography-findings-in-patients-with-resected-pulmonary-adenocarcinoma
#15
Danyun Wang, Ning Yan, Xudong Yang, Yuan Ge, Dedong Xu, Guangyuan Shao, Zhongmin Peng
Objective: To investigate the correlation between epidermal growth factor receptor (EGFR) mutation and the histologic subtypes features or computed tomography (CT) findings in patients with resected pulmonary adenocarcinoma. Materials and Methods: We retrospectively reviewed 153 patients underwent surgical resected pulmonary adenocarcinoma. EGFR mutations were detected using the amplification refractory mutation system. Histologic subtype was classified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society pulmonary adenocarcinoma classification...
January 2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29480526/lysophosphatidic-acid-induced-increase-in-adult-hippocampal-neurogenesis-facilitates-the-forgetting-of-cocaine-contextual-memory
#16
David Ladrón de Guevara-Miranda, Román Darío Moreno-Fernández, Sara Gil-Rodríguez, Cristina Rosell-Valle, Guillermo Estivill-Torrús, Antonia Serrano, Francisco J Pavón, Fernando Rodríguez de Fonseca, Luis J Santín, Estela Castilla-Ortega
Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction...
February 26, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29479307/lpar2b-controls-lateral-line-tissue-size-by-regulating-yap1-activity-in-zebrafish
#17
Xueqian Wang, Haitao Hou, Kaida Song, Zhiqiang Zhang, Shuqiang Zhang, Ying Cao, Liming Chen, Qing Sang, Fang Lin, Hui Xu
LPA signaling plays important roles during cell migration and proliferation in normal and pathological conditions. However, its role during sensory organ development remains unknown. Here we show a LPA receptor Lpar2b is expressed in the posterior lateral line primordium (pLLP) and mechanosensory organs called neuromasts (NMs) in zebrafish embryos. Lpar2b loss-of-function significantly reduces the number of NMs and hair cells in the posterior lateral line (pLL). Further analysis reveals that Lpar2b regulates the patterning and tissue size of the pLLP...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29466791/lysophosphatidic-acid-induces-ligamentum-flavum-hypertrophy-through-the-lpar1-akt-pathway
#18
Tangjun Zhou, Lin Du, Chen Chen, Chen Han, Xunlin Li, An Qin, Changqing Zhao, Kai Zhang, Jie Zhao
BACKGROUND/AIMS: Hypertrophic ligamentum flavum (LF) is a major cause of lumbar spinal stenosis. Our previous work showed that high levels of lysophosphatidic acid (LPA) expression are positively correlated with LF hypertrophy. This study aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied LPAR1 expression in human LF cells using PCR and western blotting. Cell viability cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1 knockdown or overexpression LF cells...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29415171/osteoglycin-attenuates-cardiac-fibrosis-by-suppressing-cardiac-myofibroblast-proliferation-and-migration-through-antagonizing-lysophosphatidic-acid-3-matrix-metalloproteinase-2-epidermal-growth-factor-receptor-signalling
#19
Caojian Zuo, Xiaodong Li, Jun Huang, Dongrui Chen, Kaida Ji, Yan Yang, Tingyan Xu, Dingliang Zhu, Chen Yan, Pingjin Gao
Aims: Cardiac myofibroblasts (CMFs) play a crucial role in the progression of pathological fibrotic cardiac remodelling. The expression of osteoglycin (OGN) is increased in diseased hearts; however, the role of OGN in pathological cardiac remodelling is not understood. Here, we sought to determine the effect of OGN on cardiac interstitial fibrosis and investigate the molecular mechanisms of OGN in CMF activation and matrix production. Methods and results: We found that OGN expression was significantly upregulated in mouse hearts in response to chronic 14-day angiotensin II (Ang II) infusion...
April 1, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29412173/three-lysophosphatidic-acids-with-a-distinct-long-chain-moiety-differently-affect-cell-differentiation-of-human-colon-epithelial-cells-to-goblet-cells
#20
Mayumi Hidaka, Mai Nishihara, Akira Tokumura
AIM: The intestinal mucus layer helps maintain intestinal homeostasis. In this study, we investigated the effects of lysophosphatidic acids (LPA) on differentiation of human colon carcinoma cell line, HT-29, to goblet cells with and without sodium butyrate, a known differentiation factor for intestinal cells. MAIN METHODS: Number and average size of cells with goblet-like morphology in five photographs per dish were measured for assessment of differentiation of HT-29 cells to goblet cells as well as their relative portion of surface of to whole surface area of the photograph...
March 15, 2018: Life Sciences
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