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Lysophosphatidic acid

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https://www.readbyqxmd.com/read/28616586/the-autotaxin-lysophosphatidic-acid-pathway-emerges-as-a-therapeutic-target-to-prevent-liver-cancer
#1
Derek J Erstad, Andrew M Tager, Yujin Hoshida, Bryan C Fuchs
Using transcriptome meta-analysis, we recently identified the autotaxin (ATX)-lysophosphatidic acid (LPA) pathway as a regulator of hepatocellular carcinoma (HCC) risk in human cirrhosis patients. Pharmacological targeting of this pathway reduced fibrosis progression and HCC development in animals, identifying ATX-LPA signaling as a novel chemoprevention strategy for cirrhosis and HCC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28611684/protective-role-for-lpa3-in-cardiac-hypertrophy-induced-by-myocardial-infarction-but-not-by-isoproterenol
#2
Lin Cai, Guangpu Fan, Fang Wang, Si Liu, Tiewei Li, Xiangfeng Cong, Jerold Chun, Xi Chen
Background: We previously reported that lysophosphatidic acid (LPA) promoted cardiomyocyte hypertrophy in vitro via one of its G protein-coupled receptor subtypes, LPA3. In this study, we examined the role of LPA3 in cardiac hypertrophy induced by isoproterenol (ISO) and myocardial infarction. Methods:In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to LPA3 knocked-down, or pretreated with a β-adrenergic receptor (β-AR) antagonist (propranolol) before LPA/ISO treatment. Cardiomyocyte size and hypertrophic gene (ANP, BNP) mRNA levels were determined...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28591560/implications-of-the-lysophosphatidic-acid-signaling-axis-in-liver-cancer
#3
REVIEW
Chiara Lopane, Pasquale Agosti, Isabella Gigante, Carlo Sabbà, Antonio Mazzocca
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in western countries. The major risk factors for HCC are hepatitis C or B viruses, alcohol and metabolic disorders. The increasing risk of HCC in patients with metabolic disorders (i.e. obesity, diabetes and non-alcoholic steatohepatitis/NASH) regardless of the presence of liver cirrhosis is becoming relevant. Nevertheless, molecular mechanisms linking these risk factors to liver oncogenesis are unclear. This review focuses on the pathogenic role of the lysophosphatidic acid (LPA) pathway in HCC, highlighting the implications of this bioactive phospholipid in liver cancer biology and metabolism and as potential therapeutic target...
June 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28590455/machine-learned-data-structures-of-lipid-marker-serum-concentrations-in-multiple-sclerosis-patients-differ-from-those-in-healthy-subjects
#4
Jörn Lötsch, Michael Thrun, Florian Lerch, Robert Brunkhorst, Susanne Schiffmann, Dominique Thomas, Irmgard Tegder, Gerd Geisslinger, Alfred Ultsch
Lipid metabolism has been suggested to be a major pathophysiological mechanism of multiple sclerosis (MS). With the increasing knowledge about lipid signaling, acquired data become increasingly complex making bioinformatics necessary in lipid research. We used unsupervised machine-learning to analyze lipid marker serum concentrations, pursuing the hypothesis that for the most relevant markers the emerging data structures will coincide with the diagnosis of MS. Machine learning was implemented as emergent self-organizing feature maps (ESOM) combined with the U*-matrix visualization technique...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28588064/autotaxin-lysophosphatidic-acid-lpa3-signaling-at-the-embryo-epithelial-boundary-controls-decidualization-pathways
#5
Shizu Aikawa, Kuniyuki Kano, Asuka Inoue, Jiao Wang, Daisuke Saigusa, Takeshi Nagamatsu, Yasushi Hirota, Tomoyuki Fujii, Soken Tsuchiya, Yoshitaka Taketomi, Yukihiko Sugimoto, Makoto Murakami, Makoto Arita, Makoto Kurano, Hitoshi Ikeda, Yutaka Yatomi, Jerold Chun, Junken Aoki
During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA3 in the uterine epithelium. Knockout of Lpar3 or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions...
June 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28583778/-physiopathology-and-management-of-cholestatic-pruritus-in-children
#6
A Thébaut, D Debray, E Gonzales
Pruritus is a disabling symptom accompanying chronic cholestasis. In some cases, refractory pruritus may require invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway and several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adult patients, there is no consensus in children, given the difficulty in conducting controlled clinical studies...
June 2, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28578681/dysregulation-of-lysophosphatidic-acids-in-multiple-sclerosis-and-autoimmune-encephalomyelitis
#7
K Schmitz, R Brunkhorst, N de Bruin, C A Mayer, A Häussler, N Ferreiros, S Schiffmann, M J Parnham, S Tunaru, J Chun, S Offermanns, C Foerch, K Scholich, J Vogt, S Wicker, J Lötsch, G Geisslinger, I Tegeder
Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR(1640) mice, and EAE in Lpar2 (-/-) mice...
June 2, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28578316/docosahexaenoic-acid-preserves-visual-function-by-maintaining-correct-disc-morphology-in-retinal-photoreceptor-cells
#8
Hideo Shindou, Hideto Koso, Junko Sasaki, Hiroki Nakanishi, Hiroshi Sagara, Koh M Nakagawa, Yoshikazu Takahashi, Daisuke Hishikawa, Yoshiko Iizuka-Hishikawa, Fuyuki Tokumasu, Hiroshi Noguchi, Sumiko Watanabe, Takehiko Sasaki, Takao Shimizu
Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietary DHA on visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA's effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knockout mice...
June 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28578315/lysophosphatidic-acid-acyltransferase-3-tunes-the-membrane-status-of-germ-cells-by-incorporating-docosahexaenoic-acid-during-spermatogenesis
#9
Yoshiko Iizuka-Hishikawa, Daisuke Hishikawa, Junko Sasaki, Keiyo Takubo, Motohito Goto, Katsuyuki Nagata, Hiroki Nakanishi, Hideo Shindou, Tadashi Okamura, Chizuru Ito, Kiyotaka Toshimori, Takehiko Sasaki, Takao Shimizu
Docosahexaenoic acid (DHA) is one of the essential ω-3 polyunsaturated fatty acids with a wide range of physiological roles important for human health. For example, DHA renders cell membranes more flexible and is therefore important for cellular function, but information on the mechanisms that control DHA levels in membranes is limited. Specifically, it is unclear which factors determine DHA incorporation into cell membranes and how DHA exerts biological effects. We found that lysophosphatidic acid acyltransferase 3 (LPAAT3) is required for producing DHA-containing phospholipids in various tissues, such as the testes and retina...
June 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28569176/fibroblast-like-synoviocyte-metabolism-in-the-pathogenesis-of-rheumatoid-arthritis
#10
REVIEW
Marta F Bustamante, Ricard Garcia-Carbonell, Katrijn D Whisenant, Monica Guma
An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus-cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28554198/role-of-taz-in-lysophosphatidic-acid-induced-migration-and-proliferation-of-human-adipose-derived-mesenchymal-stem-cells
#11
Won Min Mo, Yang Woo Kwon, Il Ho Jang, Eun Jung Choi, Sang Mo Kwon, Jae Ho Kim
Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs...
May 30, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28548242/enhanced-root-growth-in-phosphate-starved-arabidopsis-by-stimulating-de-novo-phospholipid-biosynthesis-through-the-overexpression-of-lysophosphatidic-acid-acyltransferase-2-lpat2
#12
Artik Elisa Angkawijaya, Van Cam Nguyen, Yuki Nakamura
Upon phosphate starvation, plants retard shoot growth but promote root development presumably to enhance phosphate assimilation from the ground. Membrane lipid remodeling is a metabolic adaptation that replaces membrane phospholipids by non-phosphorous galactolipids, thereby allowing plants to obtain scarce phosphate yet maintain the membrane structure. However, stoichiometry of this phospholipid-to-galactolipid conversion may not account for the massive demand of membrane lipids that enables active growth of roots under phosphate starvation, thereby suggesting the involvement of de novo phospholipid biosynthesis, which is not represented in the current model...
May 26, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28539367/implications-for-breast-cancer-treatment-from-increased-autotaxin-production-in-adipose-tissue-after-radiotherapy
#13
Guanmin Meng, Xiaoyun Tang, Zelei Yang, Matthew G K Benesch, Alison Marshall, David Murray, Denise G Hemmings, Frank Wuest, Todd P W McMullen, David N Brindley
We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy...
May 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28530130/injectable-graft-substitute-active-on-bone-tissue-regeneration
#14
Michela Bosetti, Alessia Borrone, Massimiliano Leigheb, Prasad Shastri, Mario Cannas
With the aim to obtain an injectable bioactive scaffold that can accelerate bone formation in sinus lift augmentation, in bony void and in fracture repair, we have developed a three-dimensional (3D) jelly collagen containing Lysophosphatidic acid (LPA) and 1α,25-Dihydroxyvitamin D3 (1,25D3). Using an in vitro 3D culture model of bone fracture we show that the contraction of the collagen gel is mediated by Rho-kinase activation in osteoblasts. This contraction was cell concentration dependent and was increased by LPA which favored apposition and fastening of bone fragments approach...
May 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28524745/actin-cytoskeleton-regulates-functional-anchorage-migration-switch-during-t-cadherin-induced-phenotype-modulation-of-vascular-smooth-muscle-cells
#15
Agne Frismantiene, Emmanouil Kyriakakis, Boris Dasen, Paul Erne, Therese J Resink, Maria Philippova
Vascular smooth muscle cell (SMC) switching between differentiated and dedifferentiated phenotypes is reversible and accompanied by morphological and functional alterations that require reconfiguration of cell-cell and cell-matrix adhesion networks. Studies attempting to explore changes in overall composition of the adhesion nexus during SMC phenotype transition are lacking. We have previously demonstrated that T-cadherin knockdown enforces SMC differentiation, whereas T-cadherin upregulation promotes SMC dedifferentiation...
May 19, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28506691/urinary-lysophopholipids-are-increased-in-diabetic-patients-with-nephropathy
#16
Jean-Sébastien Saulnier-Blache, Eva Feigerlova, Jean Michel Halimi, Pierre Gourdy, Ronan Roussel, Bruno Guerci, Aude Dupuy, Justine Bertrand-Michel, Jean-Loup Bascands, Samy Hadjadj, Joost P Schanstra
Diabetic nephropathy (DN) is a major cause of chronic kidney disease that frequently leads to end stage renal failure. Lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are lysophospholipid mediators shown to accumulate in kidney and to promote renal inflammation and tubulo-interstitial fibrosis in diabetic rodent models. Here we assessed whether LPA and LPC were associated to the development of nephropathy in diabetic human patients. Several molecular species of LPA and LPC were quantified by LC/MS-MS in urine and plasma from type 2 diabetic patients with (cases; n=41) or without (controls, n=41) nephropathy symptoms (micro/macro-albuminuria and eGFR<60ml/min/1...
July 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#17
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...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28496416/lysophosphatidic-acid-is-associated-with-atherosclerotic-plaque-instability-by-regulating-nf-%C3%AE%C2%BAb-dependent-matrix-metalloproteinase-9-expression-via-lpa2-in-macrophages
#18
Chun Gu, Fang Wang, Zhenwen Zhao, Hongyue Wang, Xiangfeng Cong, Xi Chen
Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM) degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28482552/alkaline-phosphatase-binds-tenaciously-to-titanium-implications-for-biological-surface-evaluation-following-bone-implant-retrieval
#19
J P Mansell, A I Shiel, C Harwood, D Stephens
Enhancing the performance and longevity of titanium (Ti) implants continues to be a significant developmental theme in contemporary biomaterials design. Our specific focus pertains to the surface functionalisation of Ti using the bioactive lipid, lysophosphatidic acid (LPA) and certain phosphatase-resistant analogues of LPA. Coating survivorship to a plethora of testing regimens is required to align with due regulatory process before novel biomaterials can enter clinical trials. One of the key acceptance criteria is coating retention to the physical stresses experienced during implantation...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28477431/ehrho1-regulates-plasma-membrane-blebbing-through-pi3-kinase-in-entamoeba-histolytica
#20
Ravi Bharadwaj, Ranjana Arya, Sudha Bhattacharya, Alok Bhattacharya
The protozoan parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries. Motility of E. histolytica is important for its pathogenesis. Blebbing is an essential process contributing to cellular motility in many systems. In mammalian cells, formation of plasma membrane blebs is regulated by Rho-GTPases through its effectors, such as ROCK, mDia1 and acto-myosin proteins. In the present study, we have illuminated the role of EhRho1 in bleb formation and motility of E...
May 6, 2017: Cellular Microbiology
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