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Seaweeds
Published in Parimelazhagan Thangaraj, Phytomedicine, 2020
L. Stanley Abraham, Vasantharaja Raguraman, R. Thirugnanasambandam, K. M. Smitha, D. Inbakandan, P. Premasudha
Several researchers report the anti-inflammatory potential of a monoacylglycerol and other two mixture of monogalactosyl diacylglycerols from Fucus spiralis exhibiting the inhibition of NO production in RAW 264.7 macrophage cells (Aikaterini et al. 2018; Lopes et al. 2014). Similarly, Kellogg et al. (2015) studied the anti-inflammatory potential of six coastal Alaskan seaweeds in RAW 264.7 cells by suppressing the mRNA expression for the production of COX-2, TNF-α, interleukin-10, nitric oxide synthase, and monocyte chemoattractant protein (Aikaterini et al. 2018).
Regulation of the Arachidonic Acid Cascade and PAF Metabolism in Reproductive Tissues
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
John M. Johnston, Noriei Maki, Marlane J. Angle, Dennis R. Hoffman
In support of the view that diacylglycerol was produced physiologically by phospholipase C, we demonstrated that diacylglycerol was produced in increased amounts in amnion tissue obtained from women in labor and that the diacylglycerol had a fatty acid composition almost identical to that of the parent phosphatidylinositol.49 This experiment provided further support for the presence of a phosphatidylinositol-specific phospholipase C in amnion tissue. The diacylglycerol produced in this tissue can be metabolized by at least two pathways: (1) diacylglycerol lipase or (2) phosphorylation by a diacylglycerol kinase. The activity of diacylglycerol lipase in amnion tissue was shown to be highest in the microsomal fraction and specific for the ester bond at the sn-1 position, producing fatty acid and 2-monoacylglycerol.50 This diacylglycerol lipase also preferentially cleaved diacylglycerol containing arachidonoyl in the sn-2 position. Monoacylglycerol lipase activity was also demonstrated in the cytosolic fraction of amnion tissue.50 The specific activity of monoacylglycerol lipase was significantly greater than that of diacylglycerol lipase and preferentially catalyzed the hydrolysis of 2-monoacylglycerol containing an arachidonoyl group. Based on the subcellular distribution and the effects of various inhibitors, it was concluded that monoacylglycerol lipase and diacylglycerol lipase in fetal membranes and decidua tissue were two distinct enzyme activities.
The Roles and Regulation of Prostaglandins within the Uterus
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Murray D. Mitchell, Sharlene Adamson, Curtis Coulam, Roberto J. Romero, Sarah Lundin-Schiller, Michael S. Trautman
How is the release of arachidonic acid from these glycerophospholipids controlled? Regulation of the activities of phospholipases A2 and C is an obvious method. In amnion there is a phospholipase A2 that is calcium dependent and has a substrate preference for phosphatidylethanolamine containing arachidonic acid.31 This is consistent with the release of arachidonic acid from phosphatidylethanolamine in amnion during labor. There is also a phosphatidylinositol-specific phospholipase C in amnion that is calcium dependent.32,33 Moreover, diacylglycerol and monoacylglycerol lipase activities have been detected in amnion.34 This is consistent with the release of arachidonic acid from phosphatidylinositol during early labor. The simplest mechanism for arachidonic acid release (and thence prostaglandin generation) in labor would be increasing the activities of the enzymes described above. Assay of the specific activities of these enzymes under optimal conditions at term before and after labor, however, has not revealed a significant change in the specific activities of the enzymes in uterine tissues.35
Advances in luminescence-based technologies for drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Bolormaa Baljinnyam, Michael Ronzetti, Anton Simeonov
Other bioluminescence-based enzyme assays exploit the unique structure of luciferin and how it cannot be metabolized by many mammalian and prokaryotic enzymes. For such assays, a pro-luciferin molecule which cannot enable luminescence directly is used. It must first be converted into luciferin by another enzyme before it can be used as a substrate for a luciferase. For example, DEVD-6′-aminoluciferin is a specific substrate for protease cleavage by caspase-3 or caspase-7. The cleavage by caspase-3 and −7 liberates aminoluciferin which becomes available for the luciferase, generating a luminescence signal that is directly proportional to the caspase enzyme activity. Since the substrate is specific for caspase-3 and −7, this assay can be used in both biochemical and cell-based assays and has seen widespread adoption as a method with which to measure the population of apoptotic cells [27]. Based on the same principle, a new ultra-sensitive assay to monitor monoacylglycerol lipase activity, a promising therapeutic target involved in endocannabinoid system modulation, was recently reported [28].
Monoacylglycerol lipase deficiency in the tumor microenvironment slows tumor growth in non-small cell lung cancer
Published in OncoImmunology, 2021
Melanie Kienzl, Carina Hasenoehrl, Kathrin Maitz, Arailym Sarsembayeva, Ulrike Taschler, Paulina Valadez-Cosmes, Oliver Kindler, Dusica Ristic, Sofia Raftopoulou, Ana Santiso, Thomas Bärnthaler, Luka Brcic, Lisa Hahnefeld, Robert Gurke, Dominique Thomas, Gerd Geisslinger, Julia Kargl, Rudolf Schicho
Monoacylglycerol lipase (MGL) was characterized several decades ago as the major enzyme that hydrolyzes monoglycerides into glycerol and fatty acids (rev. in1). One of these monoglycerides is 2-arachidonoyl glycerol (2-AG),2 which has been also identified as an endocannabinoid (rev. in3). 2-AG is a full agonist at cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors, thereby causing cannabimimetic effects.4 MGL contributes to many (patho)physiological conditions, such as pain, food intake, stress, metabolic disorders, addiction, inflammation, and cancer (rev. in1). Cannabinoid receptor signaling is terminated through degradation of 2-AG by MGL, which therefore plays, aside from its lipolytic function, a major role in endocannabinoid metabolism.3 It accounts for around 85% of brain 2-AG hydrolase activity while the remaining part is degraded by enzymes like α/β-hydrolase domain containing (ABHD) 6 and 12.5 2-AG, CB1/CB2 and MGL are a chain of key regulators that operate cooperatively within the endocannabinoid system (ECS). Notably, pharmacological inhibition or genetic deletion of MGL results in the accumulation of endogenous 2-AG, but not of arachidonoyl ethanolamide (anandamide; AEA), another well-described endocannabinoid.6–9 In addition, MGL provides a large pool of arachidonic acid (AA), from which pro-inflammatory prostaglandins may be generated.10 This indicates that besides 2-AG, MGL regulates the availability of AA.8,11
Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Alessandro Deplano, Jessica Karlsson, Mona Svensson, Federica Moraca, Bruno Catalanotti, Christopher J. Fowler, Valentina Onnis
Taken together, the studies above suggest that a compound with dual-action effects towards both cyclooxygenase (COX, the primary target of NSAIDs) and FAAH (or monoacylglycerol lipase) may be a potentially useful anti-inflammatory agent lacking the problematic gastrointestinal unwanted effects associated with NSAIDs. In 2015, the Piomelli group reported the synthesis and pharmacological properties of ARN2508 ((±)−2-[3-fluoro-4-[3-(hexylcarbamoyloxy)phenyl]phenyl]propanoic acid), a compound combining the structural elements of URB597 and the NSAID flurbiprofen7,8. The compound inhibited FAAH, COX-1 and COX-2 with IC50 values of 31, 12 and 420 nM, respectively, and produced anti-inflammatory effects in vivo without causing gastric irritation7. The carbamate group in the molecule was required for (presumably irreversible) FAAH inhibition, but not for COX-inhibition5. Similar to the profens9, the compound shows substrate-selective inhibition of COX-2, being more potent when 2-AG is used as substrate than when arachidonic acid (AA) is used10.