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https://www.readbyqxmd.com/read/28324037/autotaxin-is-regulated-by-glucose-and-insulin-in-adipocytes
#1
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 present 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 co-incubation with the insulin sensitizer, rosiglitazone, prevented this response...
January 16, 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
#2
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
#3
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
https://www.readbyqxmd.com/read/28298439/selective-export-of-autotoxin-from-the-endoplasmic-reticulum
#4
Lin Lyu, Baolu Wang, Chaoyang Xiong, Xiaotian Zhang, Xiaoyan Zhang, Junjie Zhang
Autotaxin (ATX) or ecto-nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid (LPA) generation. The mechanism of ATX protein trafficking is largely unknown. Here we demonstrated that p23, a member of the p24 protein family, was the protein sorting receptor required for ER export of ATX. A di-phenylalanine (F838/F839) motif in human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28264687/hyperglycemia-enhances-arsenic-induced-platelet-and-megakaryocyte-activation
#5
Jonathan D Newman, Christina T Echagarruga, Yoscar M Ogando, Emilie Montenont, Yu Chen, Edward A Fisher, Jeffrey S Berger
OBJECTIVE: Low to moderate inorganic arsenic (iAs) exposure is independently associated with cardiovascular disease (CVD), particularly for patients with diabetes mellitus (DM). The mechanism of increased CVD risk from iAs exposure in DM has not been adequately characterized. We evaluated whether increasing concentrations of glucose enhance the effects of iAs on platelet and megakaryocyte activity, key steps in atherothrombosis. METHODS: Healthy donor whole blood was prepared in a standard fashion and incubated with sodium arsenite in a range from 0 to 10 µM...
March 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28240604/autocrine-lysophosphatidic-acid-signaling-activates-%C3%AE-catenin-and-promotes-lung-allograft-fibrosis
#6
Pengxiu Cao, Yoshiro Aoki, Linda Badri, Natalie M Walker, Casey M Manning, Amir Lagstein, Eric R Fearon, Vibha N Lama
Tissue fibrosis is the primary cause of long-term graft failure after organ transplantation. In lung allografts, progressive terminal airway fibrosis leads to an irreversible decline in lung function termed bronchiolitis obliterans syndrome (BOS). Here, we have identified an autocrine pathway linking nuclear factor of activated T cells 2 (NFAT1), autotaxin (ATX), lysophosphatidic acid (LPA), and β-catenin that contributes to progression of fibrosis in lung allografts. Mesenchymal cells (MCs) derived from fibrotic lung allografts (BOS MCs) demonstrated constitutive nuclear β-catenin expression that was dependent on autocrine ATX secretion and LPA signaling...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28236660/gene-regulatory-networking-reveals-the-molecular-cue-to-lysophosphatidic-acid-induced-metabolic-adaptations-in-ovarian-cancer-cells
#7
Upasana Ray, Shreya Roy Chowdhury, Madavan Vasudevan, Kiran Bankar, Susanta Roychoudhury, Sib Sankar Roy
Extravasation and metastatic progression are two main reasons behind the high mortality rate associated with cancer. The metastatic potential of cancer cells depends on a plethora of metabolic challenges prevailing in the tumor microenvironment. To achieve higher proliferative rates, cancer cells reprogram their metabolism, increasing glycolysis and biosynthetic activities. Just why this metabolic reprogramming predisposes cells towards increased oncogenesis remains elusive. The accumulation of myriad oncolipids in the tumor microenvironment has been shown to promote the invasiveness of cancer cells, with lysophosphatidic acid (LPA) being one such critical factor enriched in ovarian cancer (OC) patients...
February 25, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28205098/enhanced-cellular-functions-through-induction-of-lpa2-by-cisplatin-in-fibrosarcoma-ht1080-cells
#8
Kaede Takahashi, Kaori Fukushima, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is a simple biophysical lipid which interacts with at least six subtypes of G protein-coupled LPA receptors (LPA1-LPA6). In cancer cells, LPA signaling via LPA receptors is involved in the regulation of malignant properties, such as cell growth, motility, and invasion. The aim of this study was to assess whether LPA receptors regulate cellular functions of fibrosarcoma cells treated with anticancer drug. HT1080 cells were maintained by the stepwise treatment of cisplatin (CDDP) at a range of 0...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28186980/diet-induced-obesity-links-to-er-positive-breast-cancer-progression-via-lpa-pkd-1-cd36-signaling-mediated-microvascular-remodeling
#9
Liuyi Dong, Ye Yuan, Cynthia Opansky, Yiliang Chen, Irene Aguilera-Barrantes, Shiyong Wu, Rong Yuan, Qi Cao, Yee Chung Cheng, Daisy Sahoo, Roy L Silverstein, Bin Ren
Obesity increases cancer risk including breast cancer (BC). However, the direct regulatory mechanisms by which obesity promotes BC progression remain largely unknown. We show that lysophosphatidic acid/protein kinase D1 (LPA/PKD-1)-CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (DIO). We observed that the growth of an estrogen receptor (ER) positive breast cancer was markedly increased when compared to the lean control, and specifically accompanied by increased microvascular remodeling in a syngeneic BC model in female DIO mice...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176353/lysophosphatidic-acid-induced-itch-is-mediated-by-signaling-of-lpa5-receptor-phospholipase-d-and-trpa1-trpv1
#10
Hiroki Kittaka, Kunitoshi Uchida, Naomi Fukuta, Makoto Tominaga
Intractable and continuous itch sensations often accompany diseases such as atopic dermatitis, neurogenic lesions, uremia and cholestasis. Lysophosphatidic acid (LPA) is an itch mediator found in cholestatic itch patients and it induces acute itch and pain in the experimental rodent models. However, the molecular mechanism by which LPA activates peripheral sensory neurons remains unknown. In this study, we used a cheek injection method in mice to reveal that LPA induced itch-related behaviors but not pain-related behaviors...
February 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#11
Michelle J Farquhar, Isla S Humphreys, Simon A Rudge, Garrick K Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M Reynolds, Margaret Aschcroft, Peter Balfe, Thomas F Baumert, Stephanie Roessler, Michael J O Wakelam, Jane A McKeating
BACKGROUND AND AIMS: Chronic hepatitis C is a global health problem with an estimated 170 million HCV infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX) is a phospholipase with diverse roles in physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood...
January 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28117004/lipoprotein-a-evolution-possible-benefits-and-harm-genetic-and-non-genetic-factors-influencing-its-plasma-levels
#12
Peggy M Kostakou, George Hatzigeorgiou, Vana Kolovou, Sophie Mavrogeni, Genovefa D Kolovou
The limited distribution of lipoprotein (a) (Lp(a)) to humans, Old World primates and to the European hedgehog, has raised considerable interest and speculation regarding its possible physiological role. Lp(a) has variable circulating concentrations (<0.1 - >100 mg/ml) which are highly genetically determined in humans. These characteristics gave rise to several theories concerning the origins and evolution of Lp(a). Lp(a) has a protective role after injury since Lp(a) particles bind to macrophages and platelets membrane receptors, leading to fibrin activation and injury healing...
January 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28111010/blocking-lysophosphatidic-acid-receptor-1-signaling-inhibits-diabetic-nephropathy-in-db-db-mice
#13
Hui Ying Li, Yoon Sin Oh, Ji-Woong Choi, Ji Yong Jung, Hee-Sook Jun
Lysophosphatidic acid (LPA) is known to regulate various biological responses by binding to LPA receptors. The serum level of LPA is elevated in diabetes, but the involvement of LPA in the development of diabetes and its complications remains unknown. Therefore, we studied LPA signaling in diabetic nephropathy and the molecular mechanisms involved. The expression of autotaxin, an LPA synthesis enzyme, and LPA receptor 1 was significantly increased in both mesangial cells (SV40 MES13) maintained in high-glucose media and the kidney cortex of diabetic db/db mice...
January 19, 2017: Kidney International
https://www.readbyqxmd.com/read/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#14
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28073697/proliferation-of-mouse-endometrial-stromal-cells-in-culture-is-highly-sensitive-to-lysophosphatidic-acid-signaling
#15
Shizu Aikawa, Kuniyuki Kano, Asuka Inoue, Junken Aoki
Endometrial stromal cells (ESCs) proliferate rapidly both in vivo and in vitro. Here we show that proliferation of ESCs in vitro is strongly dependent on lysophosphatidic acid (LPA) signaling. LPA is produced by autotaxin (ATX) and induces various kinds of cellular processes including migration, proliferation and inhibition of cell death possibly through six G protein-coupled receptors (LPA1-6). We found that ESCs proliferated rapidly in vitro in an autocrine manner and that the proliferation was prominently suppressed by either an ATX inhibitor (ONO-8430506) or an LPA1/3 antagonist (Ki16425)...
February 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#16
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28050783/daily-intake-of-high-fat-diet-with-lysophosphatidic-acid-rich-soybean-phospholipids-augments-colon-tumorigenesis-in-kyoto-apc-delta-rats
#17
Toshihiko Tsutsumi, Manami Inoue, Yoko Okamoto, Akira Ishihara, Akira Tokumura
BACKGROUND: Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice. AIMS: The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats. METHODS: Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis...
January 3, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28040465/toll-like-receptor-2-promiscuity-is-responsible-for-the-immunostimulatory-activity-of-nucleic-acid-nanocarriers
#18
Malvina Pizzuto, Monique Gangloff, Daniel Scherman, Nicholas J Gay, Virginie Escriou, Jean-Marie Ruysschaert, Caroline Lonez
Lipopolyamines (LPAs) are cationic lipids; they interact spontaneously with nucleic acids to form lipoplexes used for gene delivery. The main hurdle to using lipoplexes in gene therapy lies in their immunostimulatory properties, so far attributed to the nucleic acid cargo, while cationic lipids were considered as inert to the immune system. Here we demonstrate for the first time that di-C18 LPAs trigger pro-inflammatory responses through Toll-like receptor 2 (TLR2) activation, and this whether they are bound to nucleic acids or not...
February 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27994056/inducible-inhibition-of-g%C3%AE-%C3%AE-reveals-localization-dependent-functions-at-the-plasma-membrane-and-golgi
#19
Lauren M Klayman, Philip B Wedegaertner
Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27993681/lysophosphatidic-acid-lpa-signaling-via-lpa4-and-lpa6-negatively-regulates-cell-motile-activities-of-colon-cancer-cells
#20
Kaede Takahashi, Kaori Fukushima, Yuka Onishi, Karin Inui, Yusuke Node, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells...
January 29, 2017: Biochemical and Biophysical Research Communications
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