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Lysophosphatidic acid

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https://www.readbyqxmd.com/read/28224240/simulation-of-cell-substrate-traction-force-dynamics-in-response-to-soluble-factors
#1
Tao Liu
Finite element (FE) simulations of contractile responses of vascular muscular thin films (vMTFs) and endothelial cells resting on an array of microposts under stimulation of soluble factors were conducted in comparison with experimental measurements reported in the literature. Two types of constitutive models were employed in the simulations, i.e. smooth muscle cell type and non-smooth muscle cell type. The time histories of the effects of soluble factors were obtained via calibration against experimental measurements of contractile responses of tissues or cells...
February 21, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28218992/differently-localized-lysophosphatidic-acid-acyltransferases-crucial-for-triacylglycerol-biosynthesis-in-the-oleaginous-alga-nannochloropsis
#2
Takashi Nobusawa, Koichi Hori, Hiroshi Mori, Ken Kurokawa, Hiroyuki Ohta
Production of renewable bioenergy will be necessary to meet rising global fossil fuel demands. Members of the marine microalgae genus Nannochloropsis produce large amounts of oils (triacylglycerols; TAGs), and this genus is regarded as one of the most promising for biodiesel production. Recent genome sequencing and transcriptomic studies on Nannochloropsis have provided a foundation for understanding its oleaginous trait, but the mechanism underlying oil accumulation remains to be clarified. Here we report Nannochloropsis knockout strains of four extraplastidic lysophosphatidic acid acyltransferases (LPAT1-4), which catalyze a major de novo biosynthetic step of TAGs and membrane lipids...
February 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28214851/lysophosphatidic-acid-promotes-epithelial-to-mesenchymal-transition-in-ovarian-cancer-cells-by-repressing-sirt1
#3
Upasana Ray, Sib Sankar Roy, Shreya Roy Chowdhury
BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) plays an essential role in the transition from early to invasive phenotype, however the underlying mechanisms still remain elusive. Herein, we propose a mechanism through which the class-III deacetylase SIRT1 regulates EMT in ovarian cancer (OC) cells. METHODS: Expression analysis was performed using Q-PCR, western blot, immunofluorescence and fluorescence-IHC study. Matrigel invasion assay was used for the invasion study...
February 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28211537/ambient-ultrafine-particle-ingestion-alters-gut-microbiota-in-association-with-increased-atherogenic-lipid-metabolites
#4
Rongsong Li, Jieping Yang, Arian Saffari, Jonathan Jacobs, Kyung In Baek, Greg Hough, Muriel H Larauche, Jianguo Ma, Nelson Jen, Nabila Moussaoui, Bill Zhou, Hanul Kang, Srinivasa Reddy, Susanne M Henning, Matthew J Campen, Joseph Pisegna, Zhaoping Li, Alan M Fogelman, Constantinos Sioutas, Mohamad Navab, Tzung K Hsiai
Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp < 0.1-0.2 μm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr(-/-)) mice on a high-fat diet were orally administered with vehicle control or UFP (40 μg/mouse/day) for 3 days a week...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205098/enhanced-cellular-functions-through-induction-of-lpa2-by-cisplatin-in-fibrosarcoma-ht1080-cells
#5
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
#6
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/28185536/a-new-anti-aging-lysophosphatidic-acid-from-arabidopsis-thaliana
#7
Yujuan Sun, Yanhui Wang, Guangfa Wang, Lan Xiang, Jianhua Qi
BACKGROUND: Aging is a risk factor of age-related diseases. With the increasing number of patients, serious consequences, and heavy economic burden, demands for drugs used to treat age-related diseases have increased. As such, anti-aging substances should be isolated to develop drugs for the prevention and treatment of age-related diseases. METHODS: In this study, a methanol extract of immature Arabidopsis thaliana seeds with coat was separated by using a K6001 yeast bioassay system...
February 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28184235/phosphatidic-acid-biosynthesis-pharmacokinetics-mechanisms-of-action-and-effect-on-strength-and-body-composition-in-resistance-trained-individuals
#8
REVIEW
Peter Bond
The mechanistic target of rapamycin complex 1 (mTORC1) has received much attention in the field of exercise physiology as a master regulator of skeletal muscle hypertrophy. The multiprotein complex is regulated by various signals such as growth factors, energy status, amino acids and mechanical stimuli. Importantly, the glycerophospholipid phosphatidic acid (PA) appears to play an important role in mTORC1 activation by mechanical stimulation. PA has been shown to modulate mTOR activity by direct binding to its FKBP12-rapamycin binding domain...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28176353/lysophosphatidic-acid-induced-itch-is-mediated-by-signaling-of-lpa5-receptor-phospholipase-d-and-trpa1-trpv1
#9
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/28168106/untargeted-metabolomics-approach-for-unraveling-robust-biomarkers-of-nutritional-status-in-fasted-gilthead-sea-bream-sparus-aurata
#10
Ruben Gil-Solsona, Jaime Nácher-Mestre, Leticia Lacalle-Bergeron, Juan Vicente Sancho, Josep Alvar Calduch-Giner, Félix Hernández, Jaume Pérez-Sánchez
A metabolomic study has been performed to identify sensitive and robust biomarkers of malnutrition in farmed fish, using gilthead sea bream (Sparus aurata) as a model. The metabolomic fingerprinting of serum from fasted fish was assessed by means of ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. More than 15,000 different m/z ions were detected and Partial Least Squares-Discriminant analysis allowed a clear differentiation between the two experimental groups (fed and 10-day fasted fish) with more than 90% of total variance explained by the two first components...
2017: PeerJ
https://www.readbyqxmd.com/read/28165241/rational-design-of-autotaxin-inhibitors-by-structural-evolution-of-endogenous-modulators
#11
Willem-Jan Keune, Frances Potjewyd, Tatjana Heidebrecht, Fernando Salgado-Polo, Simon J F Macdonald, Lakshman Chelvarajan, Ahmed Abdel Latif, Sony Soman, Andrew J Morris, Allan J B Watson, Craig Jamieson, Anastassis Perrakis
Autotaxin produces the bioactive lipid lysophosphatidic acid (LPA) and is a drug target of considerable interest for numerous pathologies. We report the expedient, structure-guided evolution of weak physiological allosteric inhibitors (bile salts) into potent competitive Autotaxin inhibitors that do not interact with the catalytic site. Functional data confirms that our lead compound attenuates LPA mediated signaling in cells and reduces LPA synthesis in vivo, providing a promising natural product derived scaffold for drug discovery...
February 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28157379/cre-and-sre-mediate-lpa-induced-ccn1-transcription-in-mouse-aortic-smooth-muscle-cells
#12
Quanlin Dou, Feng Hao, Longsheng Sun, Xuemin Xu, Mei-Zhen Cui
Lysophosphatidic acid (LPA), one component of oxidized low-density lipoprotein (ox-LDL), is a potent bioactive phospholipid. Our recent data reveal that LPA induces matricellular protein CCN1 (also known as Cyr61) expression in aortic smooth muscle cells (SMCs) and that CCN1 bridges LPA and integrin signaling pathways leading to SMC migration. Whether and how LPA regulates the transcriptional machinery of the CCN1 gene are unknown. In this study, we found that LPA markedly induces CCN1 mRNA expression in SMCs...
December 17, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28151833/lysophosphatidic-acid-signaling-is-the-definitive-mechanism-underlying-neuropathic-pain
#13
Hiroshi Ueda
No abstract text is available yet for this article.
January 31, 2017: Pain
https://www.readbyqxmd.com/read/28143894/analysis-of-glycero-lysophospholipids-in-gastric-cancerous-ascites
#14
Shigenobu Emoto, Makoto Kurano, Kuniyuki Kano, Keisuke Matsusaki, Hiroharu Yamashita, Masako Nishikawa, Koji Igarashi, Hitoshi Ikeda, Junken Aoki, Joji Kitayama, Yutaka Yatomi
Lysophosphatidic acid (LysoPA) has been proposed to be involved in the pathogenesis of various cancers. Moreover, glycero-lysophospholipids other than LysoPA are now emerging as novel lipid mediators. Therefore, we aimed to elucidate the possible involvement of glycero-lysophospholipids in the pathogenesis of gastric cancer by measuring glycero-LPLs, autotaxin, and phosphatidylserine-specific phospholipase A1 (PS-PLA1) in ascites obtained from patients with gastric cancer and those with cirrhosis (as a control)...
January 31, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#15
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/28112925/highly-potent-non-carboxylic-acid-autotaxin-inhibitors-reduce-melanoma-metastasis-and-chemotherapeutic-resistance-of-breast-cancer-stem-cells
#16
Souvik Banerjee, Derek D Norman, Sue Chin Lee, Abby L Parrill, Truc Chi T Pham, Daniel L Baker, Gabor J Tigyi, Duane D Miller
Autotaxin (ATX, aka. ENPP2) is the main source of the lipid mediator lysophosphatidic acid (LPA) in biological fluids. This study reports on inhibitors of ATX derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provide a comprehensive structure-activity relationship of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. The three most potent analogues (3a, IC50 ∼ 32 nM; 3b, IC50 ∼ 9 nM; and 14, IC50 ∼ 35 nM) inhibit ATX-dependent invasion of A2058 human melanoma cells in vitro...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28111010/blocking-lysophosphatidic-acid-receptor-1-signaling-inhibits-diabetic-nephropathy-in-db-db-mice
#17
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
#18
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
#19
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)...
January 7, 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
#20
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
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