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https://www.readbyqxmd.com/read/27883058/role-of-ectonucleotide-pyrophosphatase-phosphodiesterase-2-in-the-midline-axis-formation-of-zebrafish
#1
Frisca Frisca, Daniel Colquhoun, Yona Goldshmit, Minna-Liisa Änkö, Alice Pébay, Jan Kaslin
Lysophosphatidic acid (LPA) is a unique bioactive lysophospholipid that induces pleiotropic effects in various cell types and organisms by acting on its specific receptors. LPA is mainly synthetised extracellularly by the ectonucleotide pyrophosphatase/phosphodiesterase 2/autotaxin (enpp2). Altered LPA signalling is associated with embryonic abnormalities, suggesting critical roles for LPA during development. However, the role of LPA signalling during early embryogenesis is not well established. We demonstrate that enpp2/LPA signalling in the early zebrafish embryo results in altered axis and midline formation, defects in left right (L-R) patterning, ciliogenesis of the Kupffer's vesicle (KV), through the modulation of cell migration during gastrulation in a lpar1-3 Rho/ROCK-dependant manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883026/inhibition-of-lysophosphatidic-acid-receptors-1-and-3-attenuates-atherosclerosis-development-in-ldl-receptor-deficient-mice
#2
Eva Kritikou, Gijs H M van Puijvelde, Thomas van der Heijden, Peter J van Santbrink, Maarten Swart, Frank H Schaftenaar, Mara J Kröner, Johan Kuiper, Ilze Bot
Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864940/endogenous-lpa1-receptor-agonists-demonstrate-ligand-bias-between-calcium-and-erk-signalling-pathways-in-human-lung-fibroblasts
#3
Afrah Sattikar, Mark R Dowling, Elizabeth M Rosethorne
BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a G protein-coupled receptor (GPCR) that responds to the endogenous lipid mediator lysophosphatidic acid (1-acyl-2-hydroxy-sn-glycero-3-phosphate; LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins...
November 16, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27864362/identification-of-lysophosphatidic-acid-receptor-1-in-astroglial-cells-as-a-target-for-glial-cell-line-derived-neurotrophic-factor-expression-induced-by-antidepressants
#4
Naoto Kajitani, Kanako Miyano, Mami Okada-Tsuchioka, Hiromi Abe, Kei Itagaki, Kazue Hisaoka-Nakashima, Norimitsu Morioka, Yasuhito Uezono, Minoru Takebayashi
Preclinical and clinical evidence suggests that glial cell line-derived neurotrophic factor (GDNF) is important in the therapeutic effect of antidepressants. A previous study demonstrated that the tricyclic antidepressant amitriptyline induces Gαi/o activation, which leads to GDNF expression in astrocytes. However, the specific target expressed in astrocytes that mediates antidepressant-evoked Gαi/o activation has yet to be identified. Thus, the current study explored the possibility that antidepressant-induced Gαi/o activation depends on lysophosphatidic acid receptor 1 (LPAR1), a Gαi/o-coupled receptor...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27847440/gintonin-facilitates-catecholamine-secretion-from-the-perfused-adrenal-medulla
#5
Seung-Yeol Na, Ki-Hwan Kim, Mi-Sung Choi, Kang-Su Ha, Dong-Yoon Lim
The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M1 receptor antagonist), Ki14625 (10 µM, an LPA1/3 receptor antagonist), amiloride (1 mM, an inhibitor of Na(+)/Ca(2+) exchanger), a nicardipine (1 µM, a voltage-dependent Ca(2+) channel blocker), TMB-8 (1 µM, an intracellular Ca(2+) antagonist), and perfusion of Ca(2+)-free Krebs solution with 5mM EGTA (a Ca(2+)chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor)...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27809800/lpa-receptor-1-mediates-lpa-induced-ovarian-cancer-metastasis-an-in-vitro-and-in-vivo-study
#6
Xuechen Yu, Yuanzhen Zhang, Huijun Chen
BACKGROUND: The facts that LPA is present at high concentration in ovarian cancer patients' ascites and it may serve as a stimulator to cell migration, implicate the role of LPA in the ovarian cancer metastasis. Since LPA mediates various biological functions through its interaction with LPA receptors, we aim to investigate the correlation between the expression of LPA receptors and the metastasis of ovarian cancer. METHODS: To test whether the LPA responsiveness correlated with the metastatic capability of ovarian cancer cells, we performed LPA induced invasion assay and peritoneal metastatic colonization assay with a panel of established human ovarian cancer cell lines...
November 4, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27808166/lpa-receptor-activity-is-basal-specific-and-coincident-with-early-pregnancy-and-involution-during-mammary-gland-postnatal-development
#7
Deanna Acosta, Susmita Bagchi, Pilib Ó Broin, Daniel Hollern, Silvia E Racedo, Bernice Morrow, Rani S Sellers, John M Greally, Aaron Golden, Eran Andrechek, Teresa Wood, Cristina Montagna
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784781/autotaxin-expression-is-regulated-at-the-post-transcriptional-level-by-the-rna-binding-proteins-hur-and-auf1
#8
Shuhong Sun, Xiaotian Zhang, Lin Lyu, Xixi Li, Siliang Yao, Junjie Zhang
Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a lysophospholipid mediator that regulates cellular activities through its specific G protein-coupled receptors. The ATX-LPA axis plays an important role in various physiological and pathological processes, especially in inflammation and cancer development. Although the transcriptional regulation of ATX has been widely studied, the post-transcriptional regulation of ATX is largely unknown. In this study, we identified conserved adenylate-uridylate (AU)-rich elements in the ATX mRNA 3' untranslated region (3'UTR)...
October 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27774128/discovery-of-ono-7300243-from-a-novel-class-of-lysophosphatidic-acid-receptor-1-antagonists-from-hit-to-lead
#9
Masahiko Terakado, Hidehiro Suzuki, Kazuya Hashimura, Motoyuki Tanaka, Hideyuki Ueda, Hiroshi Kohno, Taku Fujimoto, Hiroshi Saga, Shinji Nakade, Hiromu Habashita, Yoshikazu Takaoka, Takuya Seko
Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1-6. A high throughput screen against LPA1 gave compound 7a as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH)...
October 13, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27765516/effects-of-gintonin-enriched-fraction-on-hippocampal-cell-proliferation-in-wild-type-mice-and-an-appswe-psen-1-double-tg-mouse-model-of-alzheimer-s-disease
#10
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27760754/lysophosphatidic-acid-induced-vascular-neointimal-formation-in-mouse-carotid-arteries-is-mediated-by-the-matricellular-protein-ccn1-cyr61
#11
Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27757783/overexpression-of-autotaxin-is-associated-with-human-renal-cell-carcinoma-and-bladder-carcinoma-and-their-progression
#12
Aihua Xu, Md Ahsanul Kabir Khan, Fangzhi Chen, Zhaohui Zhong, Han-Chun Chen, Yuanda Song
Autotaxin (ATX) as an important tumor cell motility-stimulating factor is upregulated in many different types of cancer. ATX, a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, possesses lysophospholipase D activity which hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and mitogen lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors, thereby regulating cell growth, migration, and survival. This study aimed to investigate the differences in gene expression pattern of ATX between cancerous and adjacent normal tissue of human renal cell carcinoma (RCC) and bladder carcinoma (BC) and find the correlation between ATX expression and clinicopathological features of both of these carcinomas...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27754255/os-36-06-osteoglycin-inhibits-hypertensive-cardiac-fibrosis-though-suppression-of-egfr-signaling
#13
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27746684/effects-of-gintonin-on-the-proliferation-migration-and-tube-formation-of-human-umbilical-vein-endothelial-cells-involvement-of-lysophosphatidic-acid-receptors-and-vascular-endothelial-growth-factor-signaling
#14
Sung-Hee Hwang, Byung-Hwan Lee, Sun-Hye Choi, Hyeon-Joong Kim, Kyung Jong Won, Hwan Myung Lee, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng...
October 2016: Journal of Ginseng Research
https://www.readbyqxmd.com/read/27738243/autotaxin-mediated-lipid-signaling-intersects-with-lif-and-bmp-signaling-to-promote-the-naive-pluripotency-transcription-factor-program
#15
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27720831/imaging-flow-cytometry-in-the-assessment-of-leukocyte-platelet-aggregates
#16
Henry Hui, Kathy A Fuller, Wendy N Erber, Matthew D Linden
Platelets are subcellular blood elements with a well-established role in haemostasis. Upon activation platelets undergo granule exocytosis, resulting in α-granule P-Selectin being expressed on the cell membrane. This allows binding of activated platelets to P-Selectin glycoprotein ligand 1 (PSGL-1) expressing leukocytes, forming leukocyte-platelet aggregates (LPAs). Whole blood flow cytometry (FCM) has demonstrated that elevated circulating LPAs (especially monocyte LPAs) are linked to atherothrombosis in high risk patients, and that activated platelet binding influences monocytes towards a pro-adhesive and pro-atherogenic phenotype...
October 5, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27681370/myelin-related-gene-silencing-mediated-by-lpa1-rho-rock-signaling-is-correlated-to-acetylation-of-nf%C3%AE%C2%BAb-in-s16-schwann-cells
#17
Ryoko Tsukahara, Hiroshi Ueda
Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin-related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA1 receptor, Rho kinase, and p300, leading to an acetylation of NFκB, which down-regulates the transcription of Sox10, MBP and MPZ genes...
September 12, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27659560/hiv-1-tat-inhibits-autotaxin-lysophospholipase-d-activity-and-modulates-oligodendrocyte-differentiation
#18
Natalie A Wheeler, Babette Fuss, Pamela E Knapp, ShiPing Zou
White matter injury has been frequently reported in HIV(+) patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation...
October 2016: ASN Neuro
https://www.readbyqxmd.com/read/27651153/lysophosphatidic-acid-provides-a-missing-link-between-osteoarthritis-and-joint-neuropathic-pain
#19
J J McDougall, S Albacete, N Schuelert, P G Mitchell, C Lin, J L Oskins, H H Bui, M G Chambers
OBJECTIVE: Emerging evidence suggests that osteoarthritis (OA) has a neuropathic component; however, the identity of the molecules responsible for this peripheral neuropathy is unknown. The aim of this study was to determine the contribution of the bioactive lipid lysophosphatidic acid (LPA) to joint neuropathy and pain. DESIGN: Male Lewis rats received an intra-articular injection of 50 μg of LPA into the knee and allowed to recover for up to 21 days. Saphenous nerve myelination was assessed by g-ratio calculation from electron micrographs and afferent nerve damage visualised by activation transcription factor-3 (ATF-3) expression...
September 17, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27646403/maternal-allergic-disease-history-affects-childhood-allergy-development-through-impairment-of-neonatal-regulatory-t-cells
#20
Shan-Shan Meng, Rong Gao, Bing-di Yan, Jin Ren, Fei Wu, Peng Chen, Jie Zhang, Li-Fang Wang, Yuan-Ming Xiao, Jing Liu
BACKGROUND: Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood. METHODS: A total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study...
September 20, 2016: Respiratory Research
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