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https://www.readbyqxmd.com/read/29128569/lysophosphatidic-acid-receptor-1-is-important-for-intestinal-epithelial-barrier-function-and-susceptibility-to-colitis
#1
Songbai Lin, Yiran Han, Kayte Jenkin, Sei-Jung Lee, Maiko Sasaki, Jan-Michael Klapproth, Peijian He, C Chris Yun
Intestinal epithelial cells form a barrier that is critical in protecting the host from the hostile luminal environment. Previously, we showed that lysophosphatidic acid receptor 1 (LPAR1) regulates proliferation of intestinal epithelial cells such that the absence of LPA1 mitigates epithelial wound healing process. This study provides evidence that LPA1 is important for the maintenance of epithelial barrier integrity. The epithelial permeability, determined by fluorescently labeled dextran flux and transepithelial resistance, is increased in Lpar1(-/-) (Lpa1(-/-)) mouse intestine...
November 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29051083/lysophosphatidic-acid-propagates-post-injury-schwann-cell-dedifferentiation-through-lpa1-signaling
#2
Fabian Szepanowski, Leon-Phillip Szepanowski, Anne K Mausberg, Christoph Kleinschnitz, Bernd C Kieseier, Mark Stettner
Lysophosphatidic acid (LPA) is a pleiotropic signaling lipid that acts as ligand for at least six specific G-protein coupled receptors. Schwann cells (SC) are known to mainly express the LPA1 receptor subtype. An emerging body of evidence has linked LPA with injury-induced peripheral nerve demyelination as well as neuropathic pain. However, the molecular mechanisms underlying its demyelinating effect have not been conclusively elucidated. We aimed to decipher the demyelinating effect in vitro as well as in vivo by studying markers of SC differentiation and dedifferentiation: Myelinated dorsal root ganglia (DRG) cultures were treated either with LPA, LPA plus AM095 (LPA1 antagonist) or vehicle...
October 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29046393/-rac1-stimulated-macropinocytosis-enhances-g%C3%AE-%C3%AF-activation-of-pi3k%C3%AE
#3
Zahra Erami, Bassem D Khalil, Gilbert Salloum, Yanhua Yao, Jaclyn LoPiccolo, Aliaksei Shymanets, Bernd Nürnberg, Anne R Bresnick, Jonathan M Backer
Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29028570/bovine-ovarian-follicular-growth-and-development-correlate-with-lysophosphatidic-acid-expression
#4
Emilia Sinderewicz, Katarzyna Grycmacher, Dorota Boruszewska, Ilona Kowalczyk-Zięba, Joanna Staszkiewicz, Tomasz Ślężak, Izabela Woclawek-Potocka
The basis of successful reproduction is proper ovarian follicular growth and development. In addition to prostaglandins and vascular endothelial growth factor, a number of novel factors are suggested as important regulators of follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This study focuses on examining the expression of these factors in granulosa and thecal cells that originate from different ovarian follicle types and their link with the expression of lysophosphatidic acid (LPA), known local regulator of reproductive functions in the cow...
September 25, 2017: Theriogenology
https://www.readbyqxmd.com/read/28943105/a549-cells-as-a-model-to-study-endogenous-lpa1-receptor-signaling-and-regulation
#5
Gabriel Carmona-Rosas, Marco A Alfonzo-Méndez, David A Hernández-Espinosa, M Teresa Romero-Ávila, J Adolfo García-Sáinz
Lysophosphatidic acid (LPA) modulates the function of many organs, including the lung. A549 is a lung carcinoma-derived cell line, frequently used as a model for type II pneumocytes. Here we show that these cells expressed messenger RNA coding for LPA1-3 receptors with the following order of abundance: LPA1 > LPA2 > LPA3 and that LPA was able to increase intracellular calcium, extracellular signal-regulated kinases 1/2 phosphorylation, and cell contraction. These effects were blocked by Ki16425, an antagonist selective for LPA1 and LPA3 receptors, and by the LPA1-selective antagonist, AM095...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28939644/role-of-lysophosphatidic-acid-and-its-receptors-in-the-kidney
#6
Frank Park, Duane Miller
Lysophosphatidic acid (LPA) is a bioactive phospholipid, which can exert diverse biological effects in various diseased states of the kidney by activating at least 6 cognate G-protein coupled receptors and its complex network of heterotrimeric G-proteins. In many models of acute and chronic kidney injury, pathological elevations in LPA promotes abnormal changes in renal tubular epithelial cell architecture by activating apoptotic signaling, recruit immune cells to the site of injury, and stimulate pro-fibrotic signaling by increasing gene transcription...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28938552/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#7
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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28928633/glutaminase-and-mmp-9-downregulation-in-cortex-and-hippocampus-of-lpa1-receptor-null-mice-correlate-with-altered-dendritic-spine-plasticity
#8
Ana Peñalver, José A Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, Mercedes Martín-Rufián, Guillermo Estivill-Torrús, Raquel Sánchez-Varo, Francisco J Alonso, Mercedes Pérez-Hernández, María I Colado, Antonia Gutiérrez, Fernando Rodríguez de Fonseca, Javier Márquez
Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28926576/receptor-for-advanced-glycation-end-products-and-world-trade-center-particulate-induced-lung-function-loss-a-case-cohort-study-and-murine-model-of-acute-particulate-exposure
#9
Erin J Caraher, Sophia Kwon, Syed H Haider, George Crowley, Audrey Lee, Minah Ebrahim, Liqun Zhang, Lung-Chi Chen, Terry Gordon, Mengling Liu, David J Prezant, Ann Marie Schmidt, Anna Nolan
World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease...
2017: PloS One
https://www.readbyqxmd.com/read/28922661/lysophosphatidic-acid-inhibits-insulin-signaling-in-primary-rat-hepatocytes-via-the-lpa3-receptor-subtype-and-is-increased-in-obesity
#10
Susann Fayyaz, Lukasz Japtok, Fabian Schumacher, Dominik Wigger, Tim Julius Schulz, Kathrin Haubold, Erich Gulbins, Heinz Völler, Burkhard Kleuser
BACKGROUND/AIMS: Obesity is a main risk factor for the development of hepatic insulin resistance and it is accompanied by adipocyte hypertrophy and an elevated expression of different adipokines such as autotaxin (ATX). ATX converts lysophosphatidylcholine to lysophosphatidic acid (LPA) and acts as the main producer of extracellular LPA. This bioactive lipid regulates a broad range of physiological and pathological responses by activation of LPA receptors (LPA1-6). METHODS: The activation of phosphatidylinositide 3-kinases (PI3K) signaling (Akt and GSK-3ß) was analyzed via western blotting in primary rat hepatocytes...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28874163/expression-of-factors-involved-in-apoptosis-and-cell-survival-is-correlated-with-enzymes-synthesizing-lysophosphatidic-acid-and-its-receptors-in-granulosa-cells-originating-from-different-types-of-bovine-ovarian-follicles
#11
Emilia Sinderewicz, Katarzyna Grycmacher, Dorota Boruszewska, Ilona Kowalczyk-Zięba, Joanna Staszkiewicz, Tomasz Ślężak, Izabela Woclawek-Potocka
BACKGROUND: Lysophosphatidic acid (LPA) regulates reproductive processes in the cow. Ovarian granulosa cells play a pivotal role in follicle growth and development. Nevertheless, the role of LPA in the local regulation of granulosa cell function in different follicle categories in the bovine ovary has not been investigated. METHODS: Ovarian follicles were divided into healthy, transitional and atretic categories. The expression levels of AX, PLA2, LPARs and factors involved in apoptosis and cell survival processes in granulosa cells in different types of follicles were measured by real-time PCR...
September 6, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28869532/cftr-nherf2-lpa%C3%A2-complex-in-the-airway-and-gut-epithelia
#12
REVIEW
Weiqiang Zhang, Zhihong Zhang, Yanhui Zhang, Anjaparavanda P Naren
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and cGMP-regulated chloride (Cl(-)) and bicarbonate (HCO₃(-)) channel localized primarily at the apical plasma membrane of epithelial cells lining the airway, gut and exocrine glands, where it is responsible for transepithelial salt and water transport. Several human diseases are associated with altered CFTR channel function. Cystic fibrosis (CF) is caused by the absence or dysfunction of CFTR channel activity, resulting from mutations in the gene...
September 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28864634/evaluation-of-the-lysophosphatidic-acid-receptor-type-1-radioligand-11-c-bmt-136088-for-lung-imaging-in-rhesus-monkeys
#13
Jean-Dominique Gallezot, Nabeel B Nabulsi, Daniel Holden, Shu-Fei Lin, David Labaree, Jim Ropchan, Soheila Najafzadeh, David J Donnelly, Kai Cao, Samuel Bonacorsi, Jon Seiders, Jeffrey Roppe, Wendy Hayes, Yiyun Huang, Shuyan Du, Richard E Carson
The lysophosphatidic acid receptor type 1 (LPA1) is one of six known receptors of the extracellular signaling molecule LPA. It mediates effects such as cell proliferation, migration and differentiation. In the lung, LPA1 is involved in pathways leading, after lung tissue injury, to pulmonary fibrosis instead of normal healing, by mediating fibroblast recruitment and vascular leak. Thus, a LPA1 positron emission tomography (PET) radiotracer may be useful to study lung fibrosis, or to develop LPA1-targeting drugs...
September 1, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28859883/analgesic-effects-of-novel-lysophosphatidic-acid-receptor-5-antagonist-as2717638-in-rodents
#14
Nobuhito Murai, Hideki Hiyama, Tetsuo Kiso, Toshihiro Sekizawa, Tomonari Watabiki, Hiromasa Oka, Toshiaki Aoki
Lysophosphatidic acid (LPA) is a bioactive lipid that acts via at least six G protein-coupled receptors, LPA receptors 1-6 (LPA1-6), for various physiological functions. We examined (1) whether LPA5 is involved in pain signaling in the spinal cord; and (2) the pharmacological effects of a novel LPA5 antagonist on intrathecal prostaglandin (PG)- and (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced allodynia, and neuropathic and inflammatory pain in rodents. Intrathecal injection of a selective LPA5 agonist, geranylgeranyl diphosphate, and a non-selective agonist, LPA, induced allodynia in wild type, but not in LPA5 knockout mice...
August 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28854359/lysophosphatidic-acid-receptor-4-activation-augments-drug-delivery-in-tumors-by-tightening-endothelial-cell-cell-contact
#15
Kazuhiro Takara, Daisuke Eino, Koji Ando, Daisuke Yasuda, Hisamichi Naito, Yohei Tsukada, Tomohiro Iba, Taku Wakabayashi, Fumitaka Muramatsu, Hiroyasu Kidoya, Shigetomo Fukuhara, Naoki Mochizuki, Satoshi Ishii, Haruhiko Kishima, Nobuyuki Takakura
Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6)...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28845427/pro-tumoural-cxcl10-cxcr3-a-autocrine-loop-in-invasive-mucinous-lung-adenocarcinoma
#16
Michaël Duruisseaux, Nathalie Rabbe, Martine Antoine, Thibault Vieira, Virginie Poulot, Jacques Cadranel, Marie Wislez
Invasive mucinous adenocarcinoma (IMA) is a mucinous variant of lepidic predominant lung adenocarcinoma (LPA) and associated with a worse prognosis. We postulated that cytokine expression would enable us to differentiate IMA from LPA in terms of prognosis and acquisition of pro-tumoural capacities. A 30-cytokine panel was assessed in bronchoalveolar lavage fluids (BALF) from IMA (n=38), LPA (n=25) and control samples (n=7). We investigated the expression of differentially expressed cytokines and splice variants of their receptors in surgical samples...
January 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28843862/altered-synaptic-phospholipid-signaling-in-prg-1-deficient-mice-induces-exploratory-behavior-and-motor-hyperactivity-resembling-psychiatric-disorders
#17
Patrick Schneider, Sandra Petzold, Angela Sommer, Robert Nitsch, Herbert Schwegler, Johannes Vogt, Thomas Roskoden
Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1(-/-)) mice and PRG-1/LPA2-receptor double knockout (PRG-1(-/-)/LPA2(-/-)) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#18
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In this study, we examined the role of LPA receptors in the regulation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activity and neuronal survival by the tetracyclic antidepressants, mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells, antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
October 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28792932/structural-insights-into-ligand-recognition-by-the-lysophosphatidic-acid-receptor-lpa6
#19
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 17, 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
#20
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
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