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Kyosei Urafuji, Manabu Arioka
In mammals, three types of intracellular phospholipase A1 (iPLA1) enzymes have been characterized and are thought to be involved in various cellular processes such as phospholipid metabolism, organelle biogenesis, and membrane trafficking. In this study we analyzed the unique iPLA1-like protein, Yor022c, in the budding yeast Saccharomyces cerevisiae. By the mass spectrometry analysis, we demonstrate that Yor022c is actually a phospholipase displaying sn-1-specific activity toward phosphatidylcholine, phosphatidylethanolamine, and phosphatidic acid, generating 2-acyl lysophospholipids...
October 13, 2016: Biochemical and Biophysical Research Communications
Takayuki Furukawa, Hirotoshi Fuda, Satoshi Miyanaga, Chinatsu Watanabe, Hitoshi Chiba, Shu-Ping Hui
Even though lysophospholipids have attracted much interest in recent years on account of their unique bioactivity, research related to lysophospholipids is usually hampered by problems associated with standard sample preparation and discrimination of regioisomers. Herein, we demonstrate a quick tin-chemistry-based synthetic route to lysophosphatidylethanolamines (LPEs) and its application in the positional analysis of hepatic LPEs in non-alcoholic steatohepatitis (NASH) model mice. We found that the preference of hepatic LPE regioisomer largely depends on the unsaturation of acyl chain in both control and NASH model mice...
October 1, 2016: Chemistry and Physics of Lipids
Pan Yan, Chin Eng Ong
1. This article aims to evaluate the potentials of using cytochrome P450 2W1 (CYP2W1) as a biomarker as well as a drug target of cancer because of its characteristic cancer-specific expression. 2. Discrepant findings comparing the expression levels of CYP2W1 in cancer and non-cancer samples were reported. In general, the expression followed a developmental pattern. The demethylation status of CpG island and the expression levels of CYP2W1 genes was positively correlated. 3. CYP2W1 was able to activate several procarcinogens, anti-cancer pro-drugs, and to metabolise many endogenous substances including fatty acids and lysophospholipids...
October 3, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Salina Gairhe, Sachindra R Joshi, Mrigendra M Bastola, Jared M McLendon, Masahiko Oka, Karen A Fagan, Ivan F McMurtry
Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH...
September 2016: Pulmonary Circulation
Junzeng Fu, Bart V J Cuppen, Paco M J Welsing, Herman van Wietmarschen, Amy C Harms, Ruud Berger, Slavik Koval, Ruth D E Fritsch-Stork, Johannes W J Bijlsma, Thomas Hankemeier, Jan van der Greef, Floris P J G Lafeber
OBJECTIVE: As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients. METHODS: Serum samples from 281 RA patients were analysed using a targeted lipidomics platform...
September 28, 2016: Inflammopharmacology
Dustin Dovala, Christopher M Rath, Qijun Hu, William S Sawyer, Steven Shia, Robert A Elling, Mark S Knapp, Louis E Metzger
Gram-negative bacteria possess a characteristic outer membrane, of which the lipid A constituent elicits a strong host immune response through the Toll-like receptor 4 complex, and acts as a component of the permeability barrier to prevent uptake of bactericidal compounds. Lipid A species comprise the bulk of the outer leaflet of the outer membrane and are produced through a multistep biosynthetic pathway conserved in most Gram-negative bacteria. The final steps in this pathway involve the secondary acylation of lipid A precursors...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Ru Fang, Xudong Zhu, Yaqin Zhu, Xing Tong, Kexue Li, Hui Bai, Xiaoyu Li, Jingjing Ben, Hanwen Zhang, Qing Yang, Qi Chen
BACKGROUND AND PURPOSE: It has been accepted that AMPK (Adenosine monophosphate-activated protein kinase) activation exhibits many beneficial effects on glucolipid metabolism. Lysophosphatidylcholine (LPC) is an important lysophospholipid which can improve blood glucose levels in diabetic mice and attenuate inflammation by activating AMPK signal pathway in macrophages. Synthetic alkylphospholipids (ALPs), such as miltefosine, is used as an alternate of LPC for the clinical application...
2016: PloS One
Athira Rohit, Mark D P Willcox, Fiona Stapleton
PURPOSE: To establish the effect of lipid supplements on tear lipid biochemistry and their influence on lens wear comfort in habitual lens wearers. METHODS: Forty habitual soft contact lens wearers were recruited to a double-masked, randomized crossover trial. An emulsion drop containing phosphatidylglycerol (Systane Balance; Alcon) and a liposomal spray containing phosphatidylcholine (Tears again; BioRevive) along with saline placebos were used three times a day for 14 days with 48 hours of washout between each intervention...
October 2016: Optometry and Vision Science: Official Publication of the American Academy of Optometry
Jason W Ashley, William D Hancock, Alexander J Nelson, Robert N Bone, Hubert M Tse, Mary Wohltmann, John Turk, Sasanka Ramanadham
Macrophages are important in innate and adaptive immunity. Macrophage participation in inflammation or tissue repair is directed by various extracellular signals and mediated by multiple intracellular pathways. Activation of group VIA phospholipase A2 (iPLA2β) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2β in peritoneal macrophage immune function by comparing WT and iPLA2β-/- mouse macrophages...
September 20, 2016: Journal of Biological Chemistry
Xinping Liu, Sung Ho Moon, Christopher M Jenkins, Harold F Sims, Richard W Gross
Eicosanoid lipids play important roles in cellular signaling as second messengers in inflammation, immune response, vascular tone, and the CNS. Biosynthesis of eicosanoid lipids proceeds via hydrolysis of esterified arachidonic acid from phospholipids followed by oxidation of the released arachidonic acid by a variety of enzymes including cyclooxygenases (COX). Herein, we demonstrate the remarkable ability of COX-2, but not COX-1, to directly oxidize 2-arachidonoyl-lysolipids, resulting in the generation of previously unknown classes of eicosanoid-lysolipids, and provide evidence that intracellular lipases can release eicosanoids from their eicosanoid-lysolipid precursors...
September 13, 2016: Cell Chemical Biology
Soo Nam Park, Moon Jin Kim, Ji Hoon Ha, Nan Hee Lee, Jino Park, Jiwon Lee, Dukha Kim, Chulsoo Yoon
2-[Tris(oleoyloxymethyl)methylamino]-1-ethane sulfonic acid (TES trioleate) is an inhibitor of phospholipase A2 (PLA2), which hydrolyzes cell membrane phospholipids to produce arachidonic acid (AA) and lysophospholipids (LysoPLs). Here, we investigated the protective effects of TES trioleate on cell damage caused by ultraviolet A (UVA) light and reactive oxygen species (ROS). Pre-incubation with 250-1000μM TES trioleate resulted in concentration-dependent protection from UVA-induced damage in HaCaT cells. Additionally, 25-1000μM TES trioleate provided protection against H2O2 in a concentration-dependent manner...
September 12, 2016: Journal of Photochemistry and Photobiology. B, Biology
Koryun Mirzoyan, Anna Baïotto, Aude Dupuy, Dimitri Marsal, Colette Denis, Claire Vinel, Pierre Sicard, Justine Bertrand-Michel, Jean-Loup Bascands, Joost P Schanstra, Julie Klein, Jean-Sébastien Saulnier-Blache
Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD...
September 17, 2016: Journal of Physiology and Biochemistry
Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Zahir Hussain, Ryouhei Yamashita, Yoko Okamoto, Toru Uyama, Naoshi Yamazaki, Tamotsu Tanaka, Akira Tokumura, Natsuo Ueda
N-Acylethanolamines form a class of lipid mediators and include an endocannabinoid arachidonoylethanolamide (anandamide), analgesic and anti-inflammatory palmitoylethanolamide, and appetite-suppressing oleoylethanolamide. In animal tissues, N-acylethanolamines are synthesized from N-acylated ethanolamine phospholipids directly by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or through multi-step pathways via N-acylethanolamine lysophospholipids. We previously reported that glycerophosphodiesterase (GDE) 4, a member of the GDE family, has lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines...
September 13, 2016: Biochimica et Biophysica Acta
John A Schmidt
Determining the abundance of phospholipids and neutral lipids in cellular membranes is paramount to understanding their biological functions. Many lipid-modifying enzymes have yet to be characterized due to limitations in substrate-product measurements and purification of membrane-bound enzymes. The method described here uses radiolabeled phospholipid substrates and cell-purified organelles to quantify phospholipid metabolism using thin-layer chromatography. This assay has the benefits of being specific and adaptable for numerous applications and systems...
2016: Methods in Molecular Biology
Irma Eloisa Monroy-Muñoz, Javier Angeles-Martinez, Rosalinda Posadas-Sánchez, Teresa Villarreal-Molina, Edith Alvarez-León, Carmina Flores-Dominguez, Guillermo Cardoso-Saldaña, Aida Medina-Urrutia, Juan Gabriel Juárez-Rojas, Carlos Posadas-Romero, Gilberto Vargas Alarcon
The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population...
September 3, 2016: Immunobiology
Wei Chen, Hongwei Lu, Jie Yang, Hong Xiang, Hui Peng
Metabolic syndrome (MetS), a clustering of components, is closely associated with the development and prognosis of cardiovascular disease and diabetes. Sphingosine 1-phosphate (S1P) is a lysophospholipid with paracrine and autocrine effects, which is associated with obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension through extracellular and intracellular signals to achieve a variety of biological functions. However, there is controversy regarding the role of S1P in MetS; the specific role played by S1P remains unclear...
October 2016: International Journal of Molecular Medicine
Daisuke Saigusa, Yasunobu Okamura, Ikuko N Motoike, Yasutake Katoh, Yasuhiro Kurosawa, Reina Saijyo, Seizo Koshiba, Jun Yasuda, Hozumi Motohashi, Junichi Sugawara, Osamu Tanabe, Kengo Kinoshita, Masayuki Yamamoto
Metabolomics is a promising avenue for biomarker discovery. Although the quality of metabolomic analyses, especially global metabolomics (G-Met) using mass spectrometry (MS), largely depends on the instrumentation, potential bottlenecks still exist at several basic levels in the metabolomics workflow. Therefore, we established a precise protocol initially for the G-Met analyses of human blood plasma to overcome some these difficulties. In our protocol, samples are deproteinized in a 96-well plate using an automated liquid-handling system, and conducted either using a UHPLC-QTOF/MS system equipped with a reverse phase column or a LC-FTMS system equipped with a normal phase column...
2016: PloS One
Markus Thieme, Detlef Zillikens, Christian D Sadik
The bioactive lysophospholipid sphingosine-1-phosphate (S1P) is best known for its activity as T cell-active chemoattractant regulating the egress of T cells from the lymph node and, consequently, the availability of T cells for migration into peripheral tissues. This physiological role of S1P is exploited by the drug fingolimod, a first-line therapy for multiple sclerosis, which "detains" T cells in the lymph nodes. In recent year, it has been elucidated that S1P exerts regulatory functions far beyond T cell egress from the lymph node...
August 30, 2016: Experimental Dermatology
Yong Chan Bae, Chi Won Choi, Kyeong Wook Nam, Ji Sun Song, Jae Woo Lee
Autogenous microfat grafting is widely used to augment depressed deformities or for other cosmetic purposes. Since the microfat survival rate is unpredictable due to absorption and calcification, previously cryopreserved fat is widely used for secondary procedures. Sphingosylphosphorylcholine (SPC) is a lysophospholipid, which has a role in several cellular responses, and is known to stimulate DNA synthesis and proliferation. Since endothelial progenitor cells (EPCs) are known to enhance the survival rate of transplanted fat tissue, the present study assessed the effects of SPC on EPCs, in order to verify its positive effects on proliferation...
October 2016: Molecular Medicine Reports
Wei Hsum Yap, Nafees Ahmed, Yang Mooi Lim
Maslinic acid is a natural pentacyclic triterpenoid which has anti-inflammatory properties. A recent study showed that secretory phospholipase A2 (sPLA2) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)-sPLA2 is found in human sera and their levels are correlated with severity of inflammation. This study aims to determine whether maslinic acid interacts with hGIIA-sPLA2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA-sPLA2 and inhibited its enzyme activity in a concentration-dependent manner...
October 2016: Lipids
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