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Diacylglycerol lipase

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https://www.readbyqxmd.com/read/28315677/rimonabant-a-selective-cannabinoid1-receptor-antagonist-protects-against-light-induced-retinal-degeneration-in-vitro-and-in-vivo
#1
Tomoyo Imamura, Kazuhiro Tsuruma, Yuki Inoue, Tomohiro Otsuka, Yuta Ohno, Shiho Ogami, Shinsaku Yamane, Masamitsu Shimazawa, Hideaki Hara
The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#2
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28223925/effects-of-intermittent-alcohol-exposure-on-emotion-and-cognition-a-potential-role-for-the-endogenous-cannabinoid-system-and-neuroinflammation
#3
Laura Sanchez-Marin, Francisco J Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodriguez de Fonseca, Antonia Serrano
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-ventral-tegmental-area-dopamine-neurons
#4
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...
March 15, 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
#5
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...
March 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28191598/diacylglycerol-kinase-%C3%AE%C2%B5-localizes-to-subsurface-cisterns-of-cerebellar-purkinje-cells
#6
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
#7
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
#8
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-tag-lipase-activity-by-esi-ms-after-one-step-esterification
#9
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 FA. We present a one-step chemical derivatization method for label-free quantification of a mixture of TAG, DAG, and MAG following lipase assay by ESI-MS. Because 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...
March 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28112679/mechanism-for-leptin-s-acute-insulin-independent-effect-to-reverse-diabetic-ketoacidosis
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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