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Recent Cannabinoid Delivery Systems
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
Natascia Bruni, Carlo Della Pepa, Simonetta Oliaro-Bosso, Daniela Gastaldi, Franco Dosio, Enrica Pessione
Overall, seven different endogenous ligands have been identified as acting within the endocannabinoid system to date. The first two endocannabinoids are the derivatives of arachidonic acid N-arachidonoyl ethanolamide (anandamide) and 2-arachidonoylglycerol [12]. A third endocannabinoid, 2-arachidonoyl glyceryl ether (noladin ether), was discovered in 2001. N-arachidonoyl dopamine, O-arachidonoyl-ethanolamide (virodhamine), docosatetraenoylethanolamide, lysophosphatidylinositol, and oleoylethanolamide have since been described as ligands of endocannabinoid receptors [7].
Phosphoinositide Metabolism
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The v-Src, v-Abl, and v-H-Ras oncoproteins contain tightly bound lipids.306 Turnover of phosphoinositides is stimulated in RSV-transformed cells and the v-Src oncoprotein phosphorylates glycerol.307,308 Evidence that phosphoinositides are involved in oncogene-induced transformation is supported by the observation that injection of a monoclonal antibody to phosphatidylinositol 4,5-bisphosphate into cells transformed by the viral oncogenes v-src, v-erb-B, or v-H-ras or by an activated c-K-ras gene, but not the v-myc oncogene, leads to inhibition of cell proliferation.309 NIH/3T3 cells transformed by various oncogenes (ras, src, sis, and abl) exhibit constitutively activated synthesis of diacylglycerol, which may result in permanent activation of protein kinase C, with alteration in the phosphorylation of cellular proteins and disturbance of endogenous mitogenic signaling pathways.81 Transformation of rodent fibroblasts by cytoplasmic (mos, raf) and membrane-associated (ras, src, met, trk), but not nuclear (myc, fos) oncoproteins may result in elevation of the cellular levels of glycerophosphoinositol (GPI).310 This elevation may be specifically associated with the transformed state of the cells and not merely with their active state of proliferation. The GPI appears to be derived from deacylation of lysophosphatidylinositol as a result of increased phospholipase A2 activity. Some aspects of the complex interactions existing between viral and cellular oncoproteins and phosphoinositide metabolism are discussed next.
Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Unlike other CYPs, CYP2W1 has a unique luminal orientation in the ER but still retains catalytic activity (Gomez et al. 2010). CYP2W1 catalyzes the oxidation of indole and shows monooxygenase activity toward 3-methylindole and chlorzoxazone, but not AA (Yoshioka et al. 2006). CYP2W1 metabolizes certain lipids including lysolecithin and their stereoisomers (Karlgren et al. 2006; Xiao and Guengerich 2012). CYP2W1 expressed in HEK 293 cells is active in the metabolism of indoline substrates and is able to activate AFB1 into a cytotoxic product (Gomez et al. 2010). Lysophospholipids including oleyl (18:1) lysophosphatidylcholine (lysolecithin), lysophosphatidylinositol, lysophosphatidylserine, lysophosphatidylglycerol, lysophosphatidylethanolamine, and lysophosphatidic acid, but not diacylphospholipids, are substrates for CYP2W1 (Xiao and Guengerich 2012). CYP2W1-mediated epoxidation and hydroxylation of 18:1 lysolecithin are considerably more efficient than for the C18:1 free fatty acid. Tumor-sepcific CYP2W1 converts duocarmycin analogs to cytotoxic metabolites and kill the cancer cells via induction of DNA damage (Travica et al. 2013). This might allow the development of a novel combined therapy of colorectal cancer that would include a tumor-specific induction of CYP2W1 followed by the treatment with CYP2W1-activated prodrug. Both CYP2W1 and 2S1 catalyze the reductive activation of the anticancer prodrug AQ4N (banoxantrone) to the topoisomerase II inhibitor AQ4 (Nishida et al. 2010). In addition, CYP2W1 can bioactivate heterocyclic amines such as 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 2-amino-3methylimidazo[4,5-f]quinoline (Eun et al. 2010), suggesting a role for CYP2W1 in carcinogenesis.
How could we forget immunometabolism in SARS-CoV2 infection or COVID-19?
Published in International Reviews of Immunology, 2021
The increased cytosolic phospholipase A2 (cPLA2) activity in PECs in severe COVID-19 patients may aggravate pulmonary inflammation as indicated (damaging membrane lipids, releasing arachidonic acid (AA), and promoting neutrophil infiltration) [110, 124]. The circulating glycerophospholipids, including phosphatidic acids (PAs), phosphatidylinositols (PIs), and phosphatidylcholines (PCs), along with their corresponding lysophospholipids, like lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), and lysophosphatidylcholine (LPC) increase due to the increase in PLA2 [110]. The increase in the plasma sphingolipid GM3 enriched exosomes in severe COVID-19 patients well correlates with the decrease in T cell count and CD4+ T cell count [110]. AA metabolism suppression occurs systemically in severe COVID-19 patients. VCAM-1 expression increases in COVID-19 patients and bilirubin (an inhibitor of VCAM-1) levels decrease. The biliverdin (oxidized bilirubin) level increases in circulation, indicating oxidative stress and ROS production [110]. The 5-hydroxy tryptophan (5-HT or oxitriptan) plasma levels also increase in COVID-19 patients indicating impaired serotonin production and altered behavior and mood in severe COVID-19 patients [110].
Mass spectrometry-based phospholipid imaging: methods and findings
Published in Expert Review of Proteomics, 2020
Al Mamun, Ariful Islam, Fumihiro Eto, Tomohito Sato, Tomoaki Kahyo, Mitsutoshi Setou
PLs are diverse in chemical structures consisting of a hydrophilic head group and one or more hydrophobic acyl chains attached to an alcohol moiety [14], and are commonly referred to glycerophospholipids (GPLs) [33]. GPLs are esters of glycerol, fatty acids, and phosphoric acid(s), where glycerol acts as the backbone. Two fatty acid chains are generally present at the sn-1 and sn-2 positions, whereas the phosphate group is linked to the sn-3 position of the glycerol backbone. The head group is attached to the phosphate group(s), and its chemical nature can be diverse, leading to different GPLs. The most common GPLs containing a single phosphate group are phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylglycerol (PG) and phosphatidic acid (PA). A subclass of GPLs is the lysophospholipids (LPLs), in which a single fatty acid is present at either sn-1 or sn-2 position of the glycerol backbone. Examples of LPLs include lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidylglycerol (LPG), and lysophosphatidylserine (LPS). Diphosphatidylglycerol, historically known as cardiolipin (CL), is a unique mitochondrial PL that contains two phosphate groups and four acyl chains linked to the glycerol backbone (Table 1).
Cannabinoids and bone regeneration
Published in Drug Metabolism Reviews, 2019
Dragos Apostu, Ondine Lucaciu, Alexandru Mester, Horea Benea, Daniel Oltean-Dan, Florin Onisor, Mihaela Baciut, Simion Bran
L-α-lysophosphatidylinositol (LPI) is a GPR55 selective agonist which inhibits mouse osteoclast formation, but stimulates human osteoclast activity (Whyte et al. 2009). Another GPR55 agonist, called O-1602, has the same action, of decreasing mouse osteoclast differentiation and activating human and mouse osteoclasts (Whyte et al. 2009).