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Lysophosphatidic acid

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https://www.readbyqxmd.com/read/29627383/lpaat%C3%AE-agpat4-deficiency-impairs-maximal-force-contractility-in-soleus-and-alters-fibre-type-in-extensor-digitorum-longus-muscle
#1
Ryan M Bradley, Darin Bloemberg, Juan J Aristizabal Henao, Ashkan Hashemi, Andrew S Mitchell, Val A Fajardo, Catherine Bellissimo, Emily B Mardian, Eric Bombardier, Marie-France Paré, Katherine A Moes, Ken D Stark, A Russell Tupling, Joe Quadrilatero, Robin E Duncan
Lysophosphatidic acid acyltransferase (LPAAT) δ/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATδ and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatδ-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates...
April 5, 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
#2
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/29620892/hydroxamic-acids-constitute-a-novel-class-of-autotaxin-inhibitors-that-exhibit-in-vivo-efficacy-in-a-pulmonary-fibrosis-model
#3
Aikaterini Nikolaou, Ioanna Ninou, Maroula G Kokotou, Eleanna Kaffe, Antreas Afantitis, Vassilis Aidinis, George Kokotos
Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) generating the lipid mediator lysophosphatidic acid (LPA). Both ATX and LPA are involved in various pathological inflammatory conditions, including fibrosis and cancer, and have attracted a great interest as medicinal targets over the last decade. Thus, the development of novel potent ATX inhibitors is of great importance. We have developed a novel class of ATX inhibitors containing the zinc binding functionality of hydroxamic acid. Such novel hydroxamic acids, that incorporate a non-natural δ-amino acid residue, exhibit high in vitro inhibitory potency over ATX (IC50 values 50-60 nM)...
April 5, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29617443/changes-in-serum-levels-of-autotaxin-with-direct-acting-antiviral-therapy-in-patients-with-chronic-hepatitis-c
#4
Tomoo Yamazaki, Satoru Joshita, Takeji Umemura, Yoko Usami, Ayumi Sugiura, Naoyuki Fujimori, Takefumi Kimura, Akihiro Matsumoto, Koji Igarashi, Masao Ota, Eiji Tanaka
Sustained virological response (SVR) rates have increased remarkably since the introduction of direct-acting antiviral agents (DAAs) for chronic hepatitis C. Autotaxin (ATX) is a secreted enzyme converting lysophosphatidylcholine to lysophosphatidic acid and a newly established biomarker for liver fibrosis. Interferon-free DAA regimens for chronic hepatitis C could improve liver stiffness in SVR patients according to several non-invasive evaluation methods, but the clinical response and significance of ATX in this context have not yet been defined...
2018: PloS One
https://www.readbyqxmd.com/read/29604964/selective-inhibition-of-histamine-evoked-ca-2-signals-by-compartmentalized-camp-in-human-bronchial-airway-smooth-muscle-cells
#5
Philippa Dale, Victoria Head, Mark R Dowling, Colin W Taylor
Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [3 H]-adenine labeling...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29604355/gintonin-a-ginseng-derived-exogenous-lysophosphatidic-acid-receptor-ligand-enhances-blood-brain-barrier-permeability-and-brain-delivery
#6
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/29583156/genome-wide-analysis-of-the-glycerol-3-phosphate-acyltransferase-gpat-gene-family-reveals-the-evolution-and-diversification-of-plant-gpats
#7
Edgar Waschburger, Franceli Rodrigues Kulcheski, Nicole Moreira Veto, Rogerio Margis, Marcia Margis-Pinheiro, Andreia Carina Turchetto-Zolet
sn-Glycerol-3-phosphate 1-O-acyltransferase (GPAT) is an important enzyme that catalyzes the transfer of an acyl group from acyl-CoA or acyl-ACP to the sn-1 or sn-2 position of sn-glycerol-3-phosphate (G3P) to generate lysophosphatidic acids (LPAs). The functional studies of GPAT in plants demonstrated its importance in controlling storage and membrane lipid. Identifying genes encoding GPAT in a variety of plant species is crucial to understand their involvement in different metabolic pathways and physiological functions...
March 19, 2018: Genetics and Molecular Biology
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
#8
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
#9
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/29557721/elevated-lysophosphatidic-acid-levels-in-the-serum-and-cerebrospinal-fluid-in-patients-with-multiple-sclerosis-therapeutic-response-and-clinical-implication
#10
Dongxiao Jiang, Weiping Ju, Xijun Wu, Xia Zhan
BACKGROUND: To date, although great effort has been made to identify biomarkers of multiple sclerosis (MS), it remains unclear whether lysophosphatidic acid (LPA) can be used as a biomarker for MS. METHODS: This study compared the LPA levels in the serum and cerebrospinal fluid (CSF) in patients with MS in relapse versus in remission and investigated the change in LPA levels in MS patients in relapse after treatment. Forty-one patients with relapsing-remitting MS (RRMS) (21 patients in relapse and 20 patients in remission) and 21 patients with non-inflammatory, non-vascular neurological diseases as controls were included in this study...
March 20, 2018: Neurological Research
https://www.readbyqxmd.com/read/29554602/lysophosphatidic-acid-increases-in-vitro-maturation-efficiency-via-upa-upar-signaling-pathway-in-cumulus-cells
#11
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/29549312/measurement-of-plasma-choline-in-acute-coronary-syndrome-importance-of-suitable-sampling-conditions-for-this-assay
#12
Ryunosuke Ohkawa, Makoto Kurano, Noboru Sakai, Tatsuya Kishimoto, Takahiro Nojiri, Koji Igarashi, Shigemi Hosogaya, Yukio Ozaki, Tomotaka Dohi, Katsumi Miyauchi, Hiroyuki Daida, Junken Aoki, Shigeo Okubo, Hitoshi Ikeda, Minoru Tozuka, Yutaka Yatomi
Blood choline has been proposed as a predictor of acute coronary syndrome (ACS), however different testing procedures might affect the choline concentration because the lysophospholipase D activity of autotaxin (ATX) can convert lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline in human blood. Although the influences of ATX on LPA levels are well known in vivo and in vitro, those on choline have not been elucidated. Therefore, we established suitable sampling conditions and evaluated the usefulness of plasma choline concentrations as a biomarker for ACS...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29518748/lipid-phosphate-phosphatase-3-in-vascular-pathophysiology
#13
REVIEW
Marco Busnelli, Stefano Manzini, Cinzia Parolini, Diana Escalante-Alcalde, Giulia Chiesa
LPP3 is an integral membrane protein belonging to a family of enzymes (LPPs) that display broad substrate specificity and catalyse dephosphorylation of several lipid substrates, including lysophosphatidic acid and sphingosine-1-phosphate. In mammals, the LPP family consists of three enzymes named LPP1, LPP2 and LPP3, which are encoded by three independent genes, PLPP1, PLPP2 and PLPP3, respectively (formerly known as PPAP2A, PPAP2C, PPAP2B). These three enzymes, in vitro, do not seem to differ for catalytic activities and substrate preferences...
April 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29500864/association-between-serum-autotaxin-or-phosphatidylserine-specific-phospholipase-a1-levels-and-melanoma
#14
Makoto Kurano, Tomomitsu Miyagaki, Takuya Miyagawa, Koji Igarashi, Satoshi Shimamoto, Hitoshi Ikeda, Junken Aoki, Shinichi Sato, Yutaka Yatomi
Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA1 ) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA1 levels and melanoma...
March 3, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29500188/metabolomics-profiles-of-hepatocellular-carcinoma-in-a-korean-prospective-cohort-the-korean-cancer-prevention-study-ii
#15
Sun Ha Jee, Minjoo Kim, Minkyung Kim, Hye Jin Yoo, Hyungyoon Kim, Keum Ji Jung, Seri Hong, Jong Ho Lee
In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident hepatocellular carcinoma (HCC group) from subjects who remained free of cancer (control group) during a mean follow-up period of 7 years with the aim of identifying valuable metabolic biomarkers for HCC. We used baseline serum samples from 75 subjects with incident HCC and 134 age- and gender-matched cancer-free subjects. Serum metabolic profiles associated with HCC incidence were investigated via metabolomics analysis...
March 2, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29497765/development-and-application-of-a-uhplc-ms-ms-metabolomics-based-comprehensive-systemic-and-tissue-specific-screening-method-for-inflammatory-oxidative-and-nitrosative-stress
#16
Johannes C Schoeman, Amy C Harms, Michel van Weeghel, Ruud Berger, Rob J Vreeken, Thomas Hankemeier
Oxidative stress and inflammation are underlying pathogenic mechanisms associated with the progression of several pathological conditions and immunological responses. Elucidating the role of signalling lipid classes, which include, among others, the isoprostanes, nitro fatty acids, prostanoids, sphingoid bases and lysophosphatidic acids, will create a snapshot of the cause and effect of inflammation and oxidative stress at the metabolic level. Here we describe a fast, sensitive, and targeted ultra-high-performance liquid chromatography-tandem mass spectrometry metabolomics method that allows the quantitative measurement and biological elucidation of 17 isoprostanes as well as their respective isomeric prostanoid mediators, three nitro fatty acids, four sphingoid mediators, and 24 lysophosphatidic acid species from serum as well as organ tissues, including liver, lung, heart, spleen, kidney and brain...
March 2, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29487344/a-metabolomics-study-of-qiliqiangxin-in-a-rat-model-of-heart-failure-a-reverse-pharmacology-approach
#17
Junzeng Fu, Liping Chang, Amy C Harms, Zhenhua Jia, Hongtao Wang, Cong Wei, Li Qiao, Shuyan Tian, Thomas Hankemeier, Yiling Wu, Mei Wang
The Chinese medicine Qiliqiangxin (QL) has been shown to have a protective role in heart failure. Here, we explore the underlying working mechanism of the key therapeutic component in QL using a rat model of heart failure. Heart failure after myocardial infarction was induced surgically and confirmed using echocardiography; a separate group of rats underwent sham surgery. The rats with heart failure were randomly assigned to receive QL, the angiotensin-converting enzyme inhibitor benazepril, or placebo groups...
February 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29480526/lysophosphatidic-acid-induced-increase-in-adult-hippocampal-neurogenesis-facilitates-the-forgetting-of-cocaine-contextual-memory
#18
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/29477472/silymarin-and-caffeine-combination-ameliorates-experimentally-induced-hepatic-fibrosis-through-down-regulation-of-lpar1-expression
#19
Salma M Eraky, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El-Gayar
AIMS: Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. MAIN METHODS: Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks...
February 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29466791/lysophosphatidic-acid-induces-ligamentum-flavum-hypertrophy-through-the-lpar1-akt-pathway
#20
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
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