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Diacylglycerol lipase

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https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-vta-dopamine-neurons
#1
Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu
Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28192193/differential-expression-of-endocannabinoid-system-related-genes-in-the-dorsal-hippocampus-following-expression-and-reinstatement-of-morphine-conditioned-place-preference-in-mice
#2
Wei Li, Cong-Li Zhang, Zheng-Guo Qiu
The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine. Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation...
February 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28191598/diacylglycerol-kinase-%C3%AE%C2%B5-localizes-to-subsurface-cisterns-of-cerebellar-purkinje-cells
#3
Yasukazu Hozumi, Hiroki Fujiwara, Kenya Kaneko, Satoshi Fujii, Matthew K Topham, Masahiko Watanabe, Kaoru Goto
Following activation of Gq protein-coupled receptors, phospholipase C yields a pair of second messengers: diacylglycerol (DG) and inositol 1,4,5-trisphosphate. Diacylglycerol kinase (DGK) phosphorylates DG to produce phosphatidic acid, another second messenger. Of the DGK family, DGKε is the only DGK isoform that exhibits substrate specificity for DG with an arachidonoyl acyl chain at the sn-2 position. Recently, we demonstrated that hydrophobic residues in the N-terminus of DGKε play an important role in targeting the endoplasmic reticulum in transfected cells...
February 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28173868/docosahexaenoic-acid-increases-accumulation-of-adipocyte-triacylglycerol-through-up-regulation-of-lipogenic-gene-expression-in-pigs
#4
Chao-Wei Huang, Yu-Jen Chen, Jui-Ting Yang, Ching-Yi Chen, Kolapo M Ajuwon, Shuen-Ei Chen, Nan-Wei Su, Yu-Shan Chen, Harry J Mersmann, Shih-Torng Ding
BACKGROUND: Changing dietary fatty acid composition in modern diet influences the prevalence of obesity. Increasing evidences suggest favorable effects of n-3 PUFA for protecting against obesity and the metabolic syndrome. However, the regulation of n-3 PUFA in adipose is still unclear. Thus, this study addressed metabolism of different dietary fats in the adipose tissue of porcine model. METHODS: Eight-week-old cross-bred pigs were randomly assigned to three groups and fed a 2% fat diet for 30 days from either soybean oil (SBO), docosahexaenoic acid (DHA) or beef tallow...
February 7, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28130414/regulation-and-physiological-functions-of-mammalian-phospholipase-c
#5
REVIEW
Yoshikazu Nakamura, Kiyoko Fukami
PHOSPHOLIPASE C PLC IS A KEY ENZYME IN PHOSPHOINOSITIDE METABOLISM PLC HYDROLYSES PHOSPHATIDYLINOSITOL 4,5-BIS-PHOSPHATE TO GENERATE 2 SECOND MESSENGERS, INOSITOL 1,4,5-TRISPHOSPHATE AND DIACYLGLYCEROL, THAT GENERATE DIVERSE CELLULAR RESPONSES PLC IS ACTIVATED BY VARIOUS SIGNALLING MOLECULES, INCLUDING CA2+, HETEROMETRIC G PROTEINS, SMALL G PROTEINS, AND RECEPTOR/NON-RECEPTOR TYROSINE KINASES IN ADDITION TO THEIR ENZYMATIC ACTIVITY, SOME PLC SUBTYPES ALSO FUNCTION AS A GUANINE NUCLEOTIDE EXCHANGE FACTOR, GTPASE-ACTIVATING PROTEIN, AND ADAPTOR PROTEIN, INDEPENDENT OF THEIR LIPASE ACTIVITY THERE ARE 13 PLC ISOZYMES IN MAMMALS, AND THEY ARE CATEGORIZED INTO 6 CLASSES BASED ON STRUCTURE GENERATION AND ANALYSIS OF GENETICALLY MODIFIED MICE HAS REVEALED THE UNEXPECTEDLY DIVERSE PHYSIOLOGICAL FUNCTIONS OF PLC ISOZYMES ALTHOUGH ALL PLC ISOZYMES CATALYZE THE SAME REACTION, EACH PLC ISOZYME HAS UNIQUE PHYSIOLOGICAL FUNCTIONS THIS REVIEW FOCUSES ON THE REGULATION AND PHYSIOLOGICAL FUNCTIONS OF PLCS...
January 27, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28119444/label-free-measurement-of-the-yeast-short-chain-triacylglycerol-lipase-activity-by-electrospray-ionization-mass-spectrometry-after-one-step-esterification
#6
Hye Jin Ham, Jongcheol Seo, Hye-Joo Yoon, Seung Koo Shin
Triacylglycerol (TAG) lipases hydrolyze ester bonds in TAG and release diacylglycerol (DAG), monoacylglycerol (MAG) and fatty acid. We present a one-step chemical derivatization method for label-free quantification of a mixture of TAG, DAG, and MAG following lipase assay by electrospray ionization mass spectrometry. Since the ionization efficiencies of TAG, DAG, and MAG are not identical, lipase reaction products, DAG and MAG, are derivatized to TAG species by esterifying their hydroxyl groups, using acyl chloride whose acyl chain contains one less (or one more) -CH2 group than that of substrate TAG...
January 24, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28112679/mechanism-for-leptin-s-acute-insulin-independent-effect-to-reverse-diabetic-ketoacidosis
#7
Rachel J Perry, Liang Peng, Abudukadier Abulizi, Lynn Kennedy, Gary W Cline, Gerald I Shulman
The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28099843/human-carboxylesterase-2-reverses-obesity-induced-diacylglycerol-accumulation-and-glucose-intolerance
#8
Maxwell A Ruby, Julie Massart, Devon M Hunerdosse, Milena Schönke, Jorge C Correia, Sharon M Louie, Jorge L Ruas, Erik Näslund, Daniel K Nomura, Juleen R Zierath
Serine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling to assess the functional level of serine hydrolases in liver biopsies from lean and obese humans in order to gain mechanistic insight into the pathophysiology of metabolic disease. We identified reduced hepatic activity of carboxylesterase 2 (CES2) and arylacetamide deacetylase (AADAC) in human obesity. In primary human hepatocytes, CES2 knockdown impaired glucose storage and lipid oxidation...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28081221/dietary-lipid-sources-influence-fatty-acid-composition-in-tissue-of-large-yellow-croaker-larmichthys-crocea-by-regulating-triacylglycerol-synthesis-and-catabolism-at-the-transcriptional-level
#9
Hong Qiu, Min Jin, Yi Li, You Lu, Yingmei Hou, Qicun Zhou
An 8-week feeding trial was conducted to evaluate the effects of dietary lipid sources on growth performance, fatty acid composition, rate-limiting enzyme activities and gene expression related to lipid metabolism in large yellow croaker (Larmichthys crocea). Five iso-nitrogenous and iso-lipidic experimental diets were formulated to contain different lipid sources, such as fish oil (FO), soybean oil (SO), linseed oil (LO), rapeseed oil (RO) and peanut oil (PO), respectively. Triplicate groups of 50 fish (initial weight 13...
2017: PloS One
https://www.readbyqxmd.com/read/28002563/subcellular-localization-of-a-2-arachidonoyl-glycerol-signaling-cassette-in-retinal-ganglion-cell-axonal-growth-in-vitro
#10
David T Stark, Joseph Caprioli
Purpose: To investigate whether the subcellular distribution of endocannabinoid (eCB) system (ECS) components in growing RGC axons is consistent with the formation of eCB-enriched "hotspots" and the role of the ECS in RGC axonal growth. Methods: We used immunocytochemistry and image analysis to quantify axonal expression of the ECS components diacylglycerol lipase alpha (DGLα), monoacylglycerol lipase (MGL), and cannabinoid receptor type 1 (CB1R) in a mouse retinal explant model...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27999963/identification-of-an-endocannabinoid-system-in-the-rat-pars-tuberalis-a-possible-interface-in-the-hypothalamic-pituitary-adrenal-system
#11
Arsalan Jafarpour, Faramarz Dehghani, Horst-Werner Korf
Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research...
December 20, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27992221/triazole-ureas-act-as-diacylglycerol-lipase-inhibitors-and-prevent-fasting-induced-refeeding
#12
Hui Deng, Sander Kooijman, Adrianus M C H van den Nieuwendijk, Daisuke Ogasawara, Tom van der Wel, Floris van Dalen, Marc P Baggelaar, Freek J Janssen, Richard J B H N van den Berg, Hans den Dulk, Benjamin F Cravatt, Herman S Overkleeft, Patrick C N Rensen, Mario van der Stelt
Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold...
December 19, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27911408/defining-substrate-specificities-for-lipase-and-phospholipase-candidates
#13
Diana X Sahonero-Canavesi, Maritza Zavaleta-Pastor, Lourdes Martínez-Aguilar, Isabel M López-Lara, Otto Geiger
Microorganisms produce a wide spectrum of (phospho)lipases that are secreted in order to make external substrates available for the organism. Alternatively, other (phospho)lipases may be physically associated with the producing organism causing a turnover of intrinsic lipids and frequently giving rise to a remodeling of the cellular membranes. Although potential (phospho)lipases can be predicted with a number of algorithms when the gene/protein sequence is available, experimental proof of the enzyme activities, substrate specificities, and potential physiological functions has frequently not been obtained...
November 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27871072/testosterone-rapidly-augments-retrograde-endocannabinoid-signaling-in-proopiomelanocortin-neurons-to-suppress-glutamatergic-input-from-steroidogenic-factor-1-neurons-via-upregulation-of-diacylglycerol-lipase-%C3%AE
#14
Kristie Conde, Carolina Fabelo, William C Krause, Robert Propst, Jordan Goethel, Daniel Fischer, Jin Hur, Cecilia Meza, Holly A Ingraham, Edward J Wagner
No abstract text is available yet for this article.
November 21, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/27784678/oxyradical-stress-increases-the-biosynthesis-of-2-arachidonoylglycerol-involvement-of-nadph-oxidase
#15
Anberitha T Matthews, Jung Hwa Lee, Abdolsamad Borazjani, Lee C Mangum, Xiang Hou, Matthew K Ross
NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-β (DAGL-β), the 2-AG biosynthetic enzyme...
December 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27778288/competitive-abpp-of-serine-hydrolases-a-case-study-on-dagl-alpha
#16
Marc P Baggelaar, Mario Van der Stelt
Competitive activity-based protein profiling is a highly efficient chemical biology technique to determine target engagement and selectivity profiles of enzyme inhibitors in complex proteomes. Fluorophosphonate-based fluorescent inhibitors are widely used as broad-spectrum probes for serine hydrolases. However, diacylglycerol lipase-α is not labeled by fluorophosphonate-based probes. To overcome this problem, we have developed a tailor-made activity-based probe that reacts with diacylglycerol lipase-α. Here we describe a case study in which we apply competitive activity-based protein profiling using a broad-spectrum and a tailor-made activity-based probe to establish selectivity and activity profiles of inhibitors targeting diacylglycerol lipase-α in the mouse brain proteome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27775008/coordinated-regulation-of-endocannabinoid-mediated-retrograde-synaptic-suppression-in-the-cerebellum-by-neuronal-and-astrocytic-monoacylglycerol-lipase
#17
Xiaojie Liu, Yao Chen, Casey R Vickstrom, Yan Li, Andreu Viader, Benjamin F Cravatt, Qing-Song Liu
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic depression including depolarization-induced suppression of excitation (DSE) and inhibition (DSI). 2-AG is degraded primarily by monoacylglycerol lipase (MAGL), which is expressed in neurons and astrocytes. Using knockout mice in which MAGL is deleted globally or selectively in neurons or astrocytes, we investigated the relative contribution of neuronal and astrocytic MAGL to the termination of DSE and DSI in Purkinje cells (PCs) in cerebellar slices...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27766867/therapeutic-potential-of-fatty-acid-amide-hydrolase-monoacylglycerol-lipase-and-n-acylethanolamine-acid-amidase-inhibitors
#18
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27751891/stearoyl-coa-desaturase-1-deficiency-reduces-lipid-accumulation-in-the-heart-by-activating-lipolysis-independently-of-peroxisome-proliferator-activated-receptor-%C3%AE
#19
Tomasz Bednarski, Adam Olichwier, Agnieszka Opasinska, Aleksandra Pyrkowska, Ana-Maria Gan, James M Ntambi, Pawel Dobrzyn
Stearoyl-CoA desaturase 1 (SCD1) has recently been shown to be a critical control point in the regulation of cardiac metabolism and function. Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of myocardial fatty acid uptake and utilization. The present study used SCD1 and PPARα double knockout (SCD1(-/-)/PPARα(-/-)) mice to test the hypothesis that PPARα is involved in metabolic changes in the heart that are caused by SCD1 downregulation/inhibition. SCD1 deficiency decreased the intracellular content of free fatty acids, triglycerides, and ceramide in the heart of SCD1(-/-) and SCD1(-/-)/PPARα(-/-) mice...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27733740/production-of-biodiesel-from-acid-oil-via-a-two-step-enzymatic-transesterification
#20
Nakyung Choi, Jeom-Sig Lee, Jieun Kwak, Junsoo Lee, In-Hwan Kim
A two-step enzymatic transesterification process in a solvent-free system has been developed as a novel approach to the production of biodiesel using acid oil from rice bran oil soapstock. The acid oil consisted of 53.7 wt% fatty acids, 2.4 wt% monoacylglycerols, 9.1 wt% diacylglycerols, 28.8 wt% triacylglycerols, and 6.0 wt% others. Three immobilized lipases were evaluated as potential biocatalysts, including Novozym 435 from Candida antarctica, Lipozyme RM IM from Rhizomucor miehei, and Lipozyme TL IM from Thermomyces lanuginosus...
November 1, 2016: Journal of Oleo Science
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