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Nerve Growth Factor and Its Receptor System in Rheumatologic Diseases and Pain Management
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Smriti K. Raychaudhuri, Siba P. Raychaudhuri
NGF activates mast cells, upregulates adhesion molecules, induces chemokines, and promotes cell trafficking. Exposure of isolated mast cells to NGF and lysophosphatidylserine (a molecule on the surface of activated platelets), but not to either factor alone, induces the release of 5-hydroxytryptamine (5-HT) [85]. This indicates that NGF sensitizes mast cells under conditions of tissue injury and inflammation. In addition to 5-HT, activated mast cells release other pain mediators, such as prostaglandins, bradykinin, histamine, ATP, and NGF itself, which stimulate nociceptor terminals and potentiate the pain response [85].
Lipids of Candida Albicans
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
R. Prasad, A. Koul, P. K. Mukherjee, M. A. Ghannoum
Aculeacin A is an antifungal that inhibits membrane-bound β-l,3-glucan synthase.33 The C. albicans mutant resistant to aculeacin A develops cross resistance to other glucan synthase inhibitors.34 Lipid analyses revealed that the aculeacin A-resistant mutant, designated as AclR-1, contained about two fold higher total lipid content as compared to the parental strain.35 The free fatty acid contents were higher, while the mono-, di- and triacylglycerol contents were lower in the mutant. The resistant strain has higher amounts of PC and low levels of PS and PE. Lysophosphatidylserine, which was undetectable in the parental strain, was present in the mutant. Among the fatty acids analyzed, saturated fatty acids (16:0 and 18:0) and monounsaturated fatty acids (18:1) were significantly higher as compared to polyunsaturated fatty acids (18:2 and 18:3). Probably, the saturated nature of lipids plays a major role in aculeacin A resistance of C. albicans35
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.
Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome
Published in Ophthalmic Genetics, 2021
Austin D. Igelman, Cristy Ku, Mariana Matioli da Palma, Michalis Georgiou, Elena R. Schiff, Byron L. Lam, Eeva-Marja Sankila, Jeeyun Ahn, Lindsey Pyers, Ajoy Vincent, Juliana Maria Ferraz Sallum, Wadih M. Zein, Jin Kyun Oh, Ramiro S. Maldonado, Joseph Ryu, Stephen H. Tsang, Michael B. Gorin, Andrew R. Webster, Michel Michaelides, Paul Yang, Mark E. Pennesi
Centrosomal protein 78 (CEP78), Centrosomal protein 250 (CEP250), arylsulfatase G (ARSG), and α/β-hydrolase domain containing 12 (ABHD12) have been previously reported as causal for atypical USH (2,4,15–25). CEP78 and CEP250 are ciliary proteins important for the Usher protein network in retinal photoreceptor cells; CEP78 acts in ciliogenesis and CEP250 is expressed on cilia and interacts with CEP78 (4,16–22). Separate from the cilia are ARSG and ABHD12. ARSG encodes a sulfatase enzyme and contains a highly conserved catalytic site (15). Only two variants in ARSG in six patients have been associated with atypical USH in the literature (23,26). ABHD12 encodes a membrane-embedded serine hydrolase that hydrolyzes oxidized phosphatidylserine which is produced in inflammatory conditions and functions as a major lysophosphatidylserine (LPS) lipase in the nervous system (27). Here, we describe the clinical, imaging, and genetic findings in 19 patients in 18 families with bi-allelic variants in CEP78, CEP250, ASRG, and ABHD12 to help characterize these rare conditions.
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).
Microparticles and cardiovascular diseases
Published in Annals of Medicine, 2019
Christos Voukalis, Eduard Shantsila, Gregory Y. H. Lip
Microparticles contain a wide variety of biological molecules as part of their phospholipid membrane or within the cytosol that they enclose (Figure 3). These molecules are proteins (signal proteins, receptors and effector proteins), lipids and nucleic acids [38–40]. Various techniques have been tried in order to characterize the components of the microparticles [41,42]. Irrespective of the origin of microparticles, the plasma membrane is negatively charged due to translocation of phospholipids such as phosphatidylserine and phosphatidylcholine from internal to external surface [43,44]. Other phospholipids of the membrane include lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine, phosphatidylethanolamine, lysophosphatidylserine and phosphatidylinositol [45]. It appears that the bi-lipid layer of the microparticles affects the attached protein activities and the general properties of the vesicles [46].