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Lysophosphatidic acid

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https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#1
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28435089/cobalt-chloride-induces-rhoa-rock-activation-and-remodeling-effect-in-h9c2-cardiomyoblasts-involvement-of-pi3k-akt-and-mapk-pathways
#2
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Chronic heart failure is a serious complication of myocardial infarction, one of the major causes of death worldwide that often leads to adverse cardiac hypertrophy and poor prognosis. Hypoxia-induced cardiac tissue remodeling is considered an important underlying etiology. This study aimed to delineate the signaling profile of RhoA/ROCK, PI3K/Akt, and MAPK and their involvement in regulation of remodeling events in cultured H9c2 cardiomyoblast cells. In addition to its growth-suppressive effect, the hypoxia-mimetic chemical, cobalt chloride (CoCl2) significantly induced RhoA kinase activation as revealed by increased MBS phosphorylation and ROCK1/2 expression in H9c2 cells...
April 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28432900/lysophosphatidic-acid-induces-expression-of-genes-in-human-oral-keratinocytes-involved-in-wound-healing
#3
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/28432124/regulation-of-neurite-morphogenesis-by-interaction-between-r7-regulator-of-g-protein-signaling-complexes-and-g-protein-subunit-g%C3%AE-13
#4
Stephanie L Scherer, Matthew D Cain, Stanley M Kanai, Kevin M Kaltenbronn, Kendall J Blumer
The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of Gi/o α-subunits, several neurological phenotypes of R7-RGS knockout mice are not readily explained by dysregulated Gi/o signaling...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28405875/acute-fasting-induces-expression-of-acylglycerophosphate-acyltransferase-agpat-enzymes-in-murine-liver-heart-and-brain
#5
Ryan M Bradley, Emily B Mardian, Katherine A Moes, Robin E Duncan
During fasting, cells increase uptake of non-esterified fatty acids (NEFA) and esterify excess into phosphatidic acid (PtdOH), the common precursor of both triacylglycerols and phospholipids, using acylglycerophosphate acyltransferases/lysophosphatidic acid acyltransferases (AGPAT/LPAAT). Knowledge of the regulation of AGPAT enzymes is important for understanding fasting adaptations. Total RNA was isolated from liver, heart, and whole brain tissue of C57BL/6J mice fed ad libitum, or fasted for 16 h. Following fasting, induction of Agpat2, 3, 4, and 5 was observed in the liver, Agpat2 and 3 in heart tissue, and Agpat1, 2, and 3 in whole brain tissue...
April 12, 2017: Lipids
https://www.readbyqxmd.com/read/28402936/lysophosphatidic-acid-lpa-as-a-pro-fibrotic-and-pro-oncogenic-factor-a-pivotal-target-to-improve-the-radiotherapy-therapeutic-index
#6
REVIEW
Chloé Rancoule, Sophie Espenel, Jane-Chloé Trone, Julien Langrand-Escure, Alexis Vallard, Amel Rehailia-Blanchard, Anis El Meddeb Hamrouni, Yaxiong Xia, Jean-Baptiste Guy, Majed Ben-Mrad, Nicolas Magné
Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index...
March 29, 2017: Oncotarget
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
#7
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
#8
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/28379166/phospholipase-d-from-loxosceles-laeta-spider-venom-induces-il-6-il-8-cxcl1-gro-%C3%AE-and-ccl2-mcp-1-production-in-human-skin-fibroblasts-and-stimulates-monocytes-migration
#9
José M Rojas, Tomás Arán-Sekul, Emmanuel Cortés, Romina Jaldín, Kely Ordenes, Patricio R Orrego, Jorge González, Jorge E Araya, Alejandro Catalán
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration...
April 5, 2017: Toxins
https://www.readbyqxmd.com/read/28377726/lysophosphatidic-acid-pretreatment-attenuates-myocardial-ischemia-reperfusion-injury-in-the-immature-hearts-of-rats
#10
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
#11
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/28375206/malpa1-null-mice-as-an-endophenotype-of-anxious-depression
#12
R D Moreno-Fernández, M Pérez-Martín, E Castilla-Ortega, C Rosell Del Valle, M I García-Fernández, J Chun, G Estivill-Torrús, F Rodríguez de Fonseca, L J Santín, C Pedraza
Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression...
April 4, 2017: Translational Psychiatry
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/28341636/relief-from-neuropathic-pain-by-blocking-of-the-platelet-activating-factor-pain-loop
#18
Hideo Shindou, Seiji Shiraishi, Suzumi M Tokuoka, Yoshikazu Takahashi, Takeshi Harayama, Takaya Abe, Kana Bando, Kanako Miyano, Yoshihiro Kita, Yasuhito Uezono, Takao Shimizu
Neuropathic pain resulting from peripheral neuronal damage is largely resistant to treatment with currently available analgesic drugs. Recently, ATP, lysophosphatidic acid, and platelet-activating factor (PAF) have been reported to play important inductive roles in neuropathic pain. In the present study, we found that pain-like behaviors resulting from partial sciatic nerve ligation (PSL) were largely attenuated by deficiency of lysophosphatidylcholine acyltransferase (LPCAT)2, which is one of the PAF biosynthetic enzymes...
March 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28328321/ultrafast-and-predictive-mass-spectrometry-based-autotaxin-assays-for-label-free-potency-screening
#19
Tom Bretschneider, Andreas Harald Luippold, Helmut Romig, Daniel Bischoff, Klaus Klinder, Paul Nicklin, Wolfgang Rist
Autotaxin (ATX) is a promising drug target for the treatment of several diseases, such as cancer and fibrosis. ATX hydrolyzes lysophosphatidyl choline (LPC) into bioactive lysophosphatidic acid (LPA). The potency of ATX inhibitors can be readily determined by using fluorescence-based LPC derivatives. While such assays are ultra-high throughput, they are prone to false positives compared to assays based on natural LPC. Here we report the development of ultrafast mass spectrometry-based ATX assays enabling the measurement of data points within 13 s, which is 10 times faster than classic liquid chromatography-mass spectrometry...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28325847/specialized-diacylglycerol-acyltransferase-contributes-to-extreme-fatty-acid-content-of-cuphea-seed-oil
#20
Umidjon Iskandarov, Jillian E Silva, Hae Jin Kim, Mariette Andersson, Rebecca E Cahoon, Keithanne Mockaitis, Edgar B Cahoon
Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn-2 and sn-3 positions of seed triacylglycerols (TAGs)...
March 21, 2017: Plant Physiology
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