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Advances in Experimental Medicine and... 2021Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have... (Review)
Review
Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have an impact on cell differentiation, proliferation, migration, and angiogenesis. Phospholipases (PLC, PLD and PLA) are essential mediators of intra- and intercellular signaling. They hydrolyze phospholipids, which are major components of cell membrane that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid. Enzymatic processing of phospholipids by phospholipases converts these molecules into lipid mediators that regulate multiple cellular processes, which in turn can promote breast cancer progression. Thus, dysregulation of phospholipases contributes to a number of human diseases, including cancer. This review describes how phospholipases regulate multiple cancer-associated cellular processes, and the interplay among different phospholipases in breast cancer. A thorough understanding of the breast cancer-associated signaling networks of phospholipases is necessary to determine whether these enzymes are potential targets for innovative therapeutic strategies.
Topics: Breast Neoplasms; Humans; Phospholipase D; Phospholipases; Phospholipids; Signal Transduction; Tumor Microenvironment; Type C Phospholipases
PubMed: 33983572
DOI: 10.1007/978-981-32-9620-6_2 -
Advances in Lipid Research 1978
Comparative Study Review
Topics: Amino Acids; Animals; Bacteria; Detergents; Kinetics; Micelles; Molecular Weight; Phospholipases; Plants; Species Specificity; Substrate Specificity
PubMed: 362867
DOI: 10.1016/b978-0-12-024916-9.50011-1 -
British Medical Bulletin Jul 1983
Review
Topics: Calcium; Fatty Acids; Glucocorticoids; Humans; Phospholipases; Phospholipases A; Type C Phospholipases
PubMed: 6354351
DOI: 10.1093/oxfordjournals.bmb.a071830 -
IUBMB Life 2006Phosphatidylcholine (PC) is a major constituent of biological membranes and a component of serum lipoproteins and pulmonary surfactants. The PC and other... (Review)
Review
Phosphatidylcholine (PC) is a major constituent of biological membranes and a component of serum lipoproteins and pulmonary surfactants. The PC and other glycerophospholipid compositions of membranes change dynamically through stimulus-dependent and independent pathways, principally by the action of two different types of enzymes; phospholipase A2 [EC 3.1.1.4] and acyl-CoA:lysophospholipid acyltransferase [EC 2.3.1.23]. Phospholipase A2 is a key enzyme that catalyzes deacylation of the sn-2 position of glycerophospholipids. This enzyme is critical in the remodeling of membrane lipids and formation of two subclasses of lipid mediators, fatty acid derivatives and lysophospholipids. Among many different subtypes of phospholipase A2 enzymes, we found that cytosolic phospholipase A2alpha (cPLA2alpha) is important in various pathological and physiological responses. Here, we summarize the phenotypes resulting from genetic ablation of cPLA2alpha, and the properties of newly discovered enzymes in the cPLA2 family. Comprehensive analysis of lipid mediators using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is useful for understanding the roles of individual mediators in physiological and pathological processes.
Topics: Animals; Cytosol; Group IV Phospholipases A2; Humans; Isoenzymes; Multigene Family; Phospholipases A; Phospholipases A2
PubMed: 16754327
DOI: 10.1080/15216540600702289 -
Molecular Medicine Today Apr 1995
Review
Topics: Acetophenones; Animals; Group II Phospholipases A2; Heparin; Humans; Inflammation; Neurotoxins; Phospholipases A; Phospholipases A2; Reptilian Proteins
PubMed: 9415130
DOI: 10.1016/1357-4310(95)80011-5 -
Journal of Lipid Research Apr 2009Signal-activated phospholipases are a recent focus of the rapidly growing field of lipid signaling. The extent of their impact on the pathways regulating diverse cell... (Review)
Review
Signal-activated phospholipases are a recent focus of the rapidly growing field of lipid signaling. The extent of their impact on the pathways regulating diverse cell functions is beginning to be appreciated. A critical step in inflammation is the attraction of leukocytes to injured or diseased tissue. Chemotaxis of leukocytes, a requisite process for monocyte and neutrophil extravasation from the blood into tissues, is a critical step for initiating and maintaining inflammation in both acute and chronic settings. Recent studies have identified new important and required roles for two signal-activated phospholipases A2 (PLA2) in regulating chemotaxis. The two intracellular phospholipases, cPLA2alpha (Group IVA) and iPLA2beta (Group VIA), act in parallel to provide distinct lipid mediators at different intracellular sites that are both required for leukocytes to migrate toward the chemokine monocyte chemoattractant protein-1. This review will summarize the separate roles of these phospholipases as well as what is currently known about the influence of two other classes of intracellular signal-activated phospholipases, phospholipase C and phospholipase D, in regulating chemotaxis in eukaryotic cells, but particularly in human monocytes. The contributions of these phospholipases to chemotaxis both in vitro and in vivo will be highlighted.
Topics: Animals; Chemotaxis, Leukocyte; Humans; Phosphoinositide Phospholipase C; Phospholipase D; Phospholipases; Phospholipases A2; Signal Transduction
PubMed: 19109234
DOI: 10.1194/jlr.R800096-JLR200 -
FASEB Journal : Official Publication of... Sep 1994Phospholipases A2 are involved in inflammatory processes such as the liberation of free arachidonic acid from the membrane pool for the biosynthesis of eicosanoids.... (Review)
Review
Phospholipases A2 are involved in inflammatory processes such as the liberation of free arachidonic acid from the membrane pool for the biosynthesis of eicosanoids. Inhibitors of these enzymes are proving useful in determining the biological roles of phospholipases A2 in complex cellular processes and may also have therapeutic potential. Inhibition of these lipolytic enzymes is more difficult to characterize as the enzymatic reaction occurs at a lipid/water interface. This review focuses on the description of a number of classes of rationally designed phospholipase A2 inhibitors. The development of a theoretical framework for the proper analysis of inhibitors is presented. Structural studies of phospholipase A2-inhibitor complexes suggest how the lipolysis reaction is catalyzed. Finally, some recent results on the use of phospholipase A2 inhibitors in living cells and tissues are revealed.
Topics: Animals; Binding, Competitive; Catalysis; Humans; Kinetics; Phospholipases A; Phospholipases A2
PubMed: 8088457
DOI: 10.1096/fasebj.8.12.8088457 -
Klinische Wochenschrift Feb 1989Acid phospholipase A1 activity in liver (rat, human) is predominantly localized in lysosomes. A minor proportion (less than 3% of the total activity) is also present in... (Review)
Review
Acid phospholipase A1 activity in liver (rat, human) is predominantly localized in lysosomes. A minor proportion (less than 3% of the total activity) is also present in the Golgi apparatus and the endoplasmic reticulum, presumably due to enzymatically active precursors of the corresponding lysosomal enzyme. Lysosomal phospholipase A1 is the most important enzyme initiating the intralysosomal catabolism of diacylphosphoglycerides. It has been purified 50,600-fold, with a yield of about 26%. The enzyme prefers phosphatidyl-ethanolamine as a substrate, which at 200 microM and pH 4.5, is hydrolysed at a rate of approximately 8.2 U/mg. Lysosomal phospholipase A1 is a glycoprotein of about 29 kDa with an isoelectric point of pH 5.3. Unspecific extralysosomal endogenous inhibitors of this enzyme are pH range, inorganic cations, and various proteins. Divalent cations are more potent inhibitors than monovalent ones. Most endogenous intra- and extracellular proteins inhibit the enzyme, the cationic species exhibiting high inhibitory potencies, glycoproteins only little. Inhibitory proteins act through their binding to the substrate. Lysosomal phospholipase A1 seems to be an important target in drug-induced lipidosis. This lipid storage disease is caused by various cationic amphiphilic drugs that are trapped intralysosomally by protonation. In lysosomes such compounds raise the pH, interact with the polar lipids to be degraded and the lysosomal lipolytic enzymes, such as phospholipase A1. These mechanisms result in impaired intralysosomal phospholipid degradation and hence in intralysosomal phospholipid accumulation.
Topics: Humans; Hydrogen-Ion Concentration; Liver; Lysosomes; Phospholipases; Phospholipases A; Phospholipases A1
PubMed: 2648056
DOI: 10.1007/BF01711337 -
Nihon Rinsho. Japanese Journal of... Feb 2001
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Annual Review of Biochemistry 1997This review focuses on two phospholipase activities involved in eukaryotic signal transduction. The action of the phosphatidylinositol-specific phospholipase C enzymes... (Review)
Review
This review focuses on two phospholipase activities involved in eukaryotic signal transduction. The action of the phosphatidylinositol-specific phospholipase C enzymes produces two well-characterized second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. This discussion emphasizes recent advances in elucidation of the mechanisms of regulation and catalysis of the various isoforms of these enzymes. These are especially related to structural information now available for a phospholipase C delta isozyme. Phospholipase D hydrolyzes phospholipids to produce phosphatidic acid and the respective head group. A perspective of selected past studies is related to emerging molecular characterization of purified and cloned phospholipases D. Evidence for various stimulatory agents (two small G protein families, protein kinase C, and phosphoinositides) suggests complex regulatory mechanisms, and some studies suggest a role for this enzyme activity in intracellular membrane traffic.
Topics: Animals; Humans; Molecular Sequence Data; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoinositide Phospholipase C; Phospholipase D; Type C Phospholipases
PubMed: 9242915
DOI: 10.1146/annurev.biochem.66.1.475