Metabolism and Function of Bioactive Ether Lipids in the Brain

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Edition: 1st
Format: Hardcover
Pub. Date: 2008-04-01
Publisher(s): Springer Verlag
List Price: $219.99

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Summary

Information on bioactive ether lipids and their involvement in neurological disorders is currently scattered throughout the literature in the form of original papers and reviews. Metabolism and Functions of Bioactive Ether Lipids in the Brain provides readers with a comprehensive description of metabolism of bioactive ether lipids in the brain, activities of enzymes involved in their metabolism, and their involvement in neurological disorders. This book will be particularly useful to neuroscience graduate students, academics, and researchers. Clinicians will find this book useful for understanding molecular aspects of neurodegeneration in acute neural trauma and neurodegenerative diseases that are mediated by plamalogen-selective phospholipases A 2 and PAF acetyl hydrolases. This monograph is the first to provide a comprehensive description of not only metabolism and role of plasmalogen and platelet activating factor in brain tissue but also the involvement of these lipids with abnormal signal transduction processes in neurological disorders. Key Features a?? Provides the neuroscience community with extensive description of ether lipids-derived lipid mediators their roles and association with neurological disorders a?? Particular attention given to the description of keys enzymes associated with the generation of ether lipid-derived lipid mediators a?? Illustrated with chemical structures and line diagrams of signal transduction pathways a?? Discusses the future direction of research on ether lipid metabolism About the Authors Akhlaq A. Farooqui is a leader in the field of bioactive ether lipids, glutamate-mediated neurotoxicity, and brain phospholipases A 2 . In collaboration with late Dr. Lloyd A. Horrocks, he discovered a plasmalogen-selective phospholipase A 2 in brain and showed its stimulation in kainate-mediated neurotoxicity and brain tissue from patients with Alzheimer disease. He has also found a decrease in plasmalogen levels in brain from Alzheimera??s disease patients. This decrease in plasmalogens is due to the stimulation of phospholipases A 2 . Akhlaq A. Farooqui has authored two monographs, Glycerophospholipids in Brain: Phospholipase A 2 in Neurological Disorders (Springer, 2006) and Neurochemical Aspects of Excitotoxicity (Springer, 2007). Tahira Farooqui is an expert on glycerophospholipid and sphingolipid metabolism and neural plasticity. She has published extensively on molecular mechanism of neuroinflammation, interactions between glycerophospholipid and sphingolipid-derived lipid mediators, and neural plasticity in the brain.

Table of Contents

Occurrence and Importance of Ether Lipids in Brainp. 1
Introductionp. 1
Classification of Ether Lipids Found in Brainp. 2
Physicochemical Properties of Ether Lipidsp. 3
Fecapentaenes: The Novel Plasmalogensp. 4
Other Ether Lipids Found in Mammalian Tissuesp. 6
Lipid Metabolism in Ether Lipid-Deficient Micep. 10
Conclusionp. 12
Referencesp. 13
Biosynthesis of Plasmalogens in Brainp. 17
General Considerations and Distribution of Plasmalogens in Brainp. 17
Biosynthesis of Plasmalogensp. 18
Dihydroxyacetone Phosphate Acyltransferasep. 20
Alkyl Dihydroxyacetone Phosphate Synthasep. 23
Acyl/alkyl Dihydroxyacetone Phosphate Reductasep. 25
Alkylglycerophosphate Acyltransferasep. 26
Alkylacyl Glycerophosphate Phosphohydrolasep. 26
CDP-Ethanolamine: Diacylglycerol Ethanolaminephosphotransferasep. 27
Plasmalogen Synthesizing Enzymes During Brain Developmentp. 28
Topology and Distribution of Plasmalogens and Enzymes Synthesizing Plasmalogensp. 29
Plasmalogens in Lipid Raftsp. 30
Plasmalogens in the Nucleusp. 30
Factors Affecting Plasmalogen Biosynthesis in Brainp. 31
Conclusionp. 32
Referencesp. 33
Catabolism of Plasmalogens in Brainp. 39
Introductionp. 39
Plasmalogen-Selective Phospholipase A2 (PlsEtn-PLA2)p. 39
Receptor-Mediated Degradation of Plasmalogensp. 44
Regulation of PlsEtn-PLA2p. 48
Turnover of Plasmalogen in Brainp. 49
Remodeling of Plasmalogens (Reacylation/Deacylation Reactions)p. 50
Degradation of Plasmalogens by Phospholipase Cp. 51
Nonenzymic Oxidation of Plasmalogens in Brainp. 51
Plasmalogen-Derived Lipid Mediators and Their Importance in Brainp. 54
Lysoplasmalogens in Brainp. 58
Conclusionp. 59
Referencesp. 59
Assay and Purification of Plasmalogen-Selective Phospholipase A2 and Lysoplasmalogenase Activitiesp. 67
Introductionp. 67
Determination of PlsEtn and PlsCho-PLA2 by Radiochemical Proceduresp. 68
Preparation of Radiolabled [3H] Plasmenylcholine (Choline Plasmalogen)p. 68
Labeling of Lysoplasmenylcholine at the Sn-2 Positionp. 70
Determination of PlsCho-PLA2 Activityp. 70
Determination of PlsEtn-PLA2 by Fluorometric Assayp. 71
Purification of Ethanolamine Plasmalogenp. 72
Labeling of Ethanolamine Plasmalogen with Pyrenesulfonyl Chloridep. 72
Determination of PlsEtn-PLA2 Activity with Pyrene-Labeled Plasmalogenp. 73
Continuous Spectrophotometric Determination of PlsEtn-PLA2p. 74
Determination of Lysoplasmalogenasep. 74
Continuous Spectrophotometric Procedure for Lysoplasmalogenasep. 75
Continuous Spectrofluorometric Procedure for Lysoplasmalogenasep. 76
Activities of Plasmalogen-Selective PLA2 in Brains of Various Animal Species and Cultured Cells of Neuronal and Glial Originp. 78
Determination of Lysoplasmalogenase Activity in Rat Liver and Brain Microsomesp. 78
Purification of Plasmalogen-Selective PLA2 from Brainp. 80
Purification of Lysoplasmalogenase from Liverp. 80
Conclusionp. 81
Referencesp. 81
Roles of Plasmalogens in Brainp. 85
Introductionp. 85
Roles of Plasmalogens in Brainp. 85
Plasmalogens as Neural Membrane Componentsp. 85
Plasmalogens as a Storage Depot for Second Messengers and Lipid Mediatorsp. 86
Plasmalogens in Regulation of Enzymic Activitiesp. 91
Plasmalogens in Membrane Fusionp. 91
Plasmalogens in Ion Transportp. 92
Plasmalogens in High-Density Lipoproteinp. 93
Plasmalogens, Cholesterol Oxidation, Efflux and Atherosclerosisp. 93
Plasmalogens and Their Antioxidant Activityp. 94
Plasmalogens and Generation of Long-Chain Aldehydesp. 97
Plasmalogens in Differentiationp. 97
Plasmalogens in the Ocular Developmentp. 98
Plasmalogens as Precursors for the Platelet-Activating Factorp. 98
Conclusionp. 99
Referencesp. 99
Involvement of Plasmalogens in Neurological Disordersp. 107
Introductionp. 107
Plasmalogens in Neurological Disordersp. 108
Plasmalogens in Ischemic Injuryp. 110
Plasmalogens in Alzheimer Diseasep. 111
Plasmalogens in Spinal Cord Injuryp. 114
Plasmalogens in Peroxisomal Disordersp. 115
Plasmalogens in Sjogren-Larsson Syndromep. 118
Plasmalogens in Malnutritionp. 119
Plasmalogens in Fetal Alcohol Syndromep. 119
Plasmalogens in Diabetic Heartp. 119
Plasmalogens in Other Neurological Disordersp. 120
Plasmalogens in Uremic Patientsp. 120
Plasmalogens in Myelin-Deficient Mutant Micep. 121
Conclusionp. 121
Referencesp. 122
Synthesis of Platelet-Activating Factor in Brainp. 129
Introductionp. 129
Biosynthesis of PAFp. 130
Remodeling Pathway (Deacylation/Reacylation Pathway)p. 130
Cytosolic Phospholipase A2 (cPLA2)p. 131
Acetyl-CoA/Lyso-PAF Acetyltransferasep. 133
CoA-Independent Transacetylasep. 135
De Novo Synthesis of PAFp. 137
1-Alkyl-2-lyso-OT-grycero-3-phosphate (Alkyllyso-GP)/Acetyl-CoA Acetyltransferasep. 138
1-Alkyl-2-acetyl-OT-grycero-3-phosphate Phosphohydrolasep. 140
1-Alkyl-2-acetyl-OT-glycerol/CDP-choline Phosphotransferasep. 140
Oxidative Fragmentation Pathway for PAF Synthesisp. 142
Regulation of PAF Synthesisp. 143
Conclusionp. 145
Referencesp. 146
Degradation of Platelet-Activating Factor in Brainp. 151
Introductionp. 151
PAF-Acetyl Hydrolases in Brain and Plasmap. 152
Purification and Properties of PAF-Acetyl Hydrolasesp. 153
Types I PAF-Acetyl Hydrolases in Mammalian Tissuesp. 154
Types II PAF-Acetyl Hydrolases in Mammalian Tissuesp. 155
PAF-Acetyl Hydrolases in Mammalian Plasmap. 156
Other PAF-Acetyl Hydrolasesp. 158
Regulation and Roles of PAF-Acetyl Hydrolases in Brainp. 159
PAF Hydrolyzing Phospholipase Cp. 164
Other PAF Hydrolyzing Lipasesp. 165
Conclusionp. 166
Referencesp. 166
Roles of Platelet-Activating Factor in Brainp. 171
Introductionp. 171
PAF Receptors in Brainp. 174
Translocation of PAF from Synthetic Site to Cell Surface Receptorsp. 175
PAF-Receptor-Mediated Signal Transductionp. 176
Roles of PAF in brainp. 179
PAF in Gene Expressionp. 179
PAF in Neural Cell Migrationp. 182
PAF in Long-Term Potentiationp. 183
PAF in Glutamate-Mediated Neurotoxicityp. 184
PAF and Calcium Influxp. 186
PAF in Neuroinflammationp. 186
PAF in Cerebral Blood Flow and Blood-Brain Barrier Permeabilityp. 187
PAF in Apoptosisp. 188
PAF in Noniceptionp. 189
PAF in Immune Responsep. 190
Conclusionp. 190
Referencesp. 191
Involvement of Platelet-Activating Factor in Neurological Disordersp. 197
Introductionp. 197
Involvement of Platelet-Activating Factor in Neurological Disordersp. 198
PAF in Ischemiap. 199
PAF in Head Injury and Spinal Cord Traumap. 200
PAF in Meningitisp. 201
PAF in HIV Infectionp. 202
PAF in Prion Diseasesp. 203
PAF in Multiple Sclerosisp. 204
PAF in Miller-Dieker Lissencephalyp. 204
PAF in Migraine Attacksp. 205
PAF in Kainic-Acid-Mediated Neurodegenerationp. 205
Involvement of PAF in Nonneural Injuriesp. 206
Consequences of Altered PAF Acetyl Hydrolase in Cardiovascular Systemp. 207
Molecular Mechanism of PAF-Mediated Neural Injuryp. 208
Clinical Application of PAF Antagonists for the Treatment of Neurological Disordersp. 210
Conclusionp. 211
Referencesp. 211
Biochemical Effects of Nonphysiological Antitumor Ether Lipidsp. 219
Introductionp. 219
Effect of AEL on Enzymes Involved in Signal Transductionp. 222
Effects of AEL on Phospholipases A2, C, and Dp. 223
Effects of AEL on Protein and Lipid Kinasesp. 224
Effect of AEL on Cellular Receptorsp. 228
Other Effects of AEL on Cellular Metabolismp. 230
Molecular Mechanism and Site of Action of AELp. 231
Conclusionp. 232
Referencesp. 232
Perspective and Directions for Future Developments on Ether Lipidsp. 237
Introductionp. 237
Interactions Among Glycerophospholipid, Sphingolipid, and Cholesterol-Derived Lipid Mediatorsp. 239
Interactions Between Ether Lipid and Sphingolipid-Derived Lipid Mediatorsp. 240
Interactions Between Sphingolipid and Cholesterol-Derived Lipid Mediatorsp. 243
Use of Lipidomics, Proteomics, and Genomics for Characterization of Enzymes, Lipid Mediators, and Signal Transduction Process in Normal and Diseased Brain Tissuesp. 244
Use of RNAi for the Treatment of Ether Lipid-Related Neurodegenerative Diseasesp. 246
Conclusionp. 248
Referencesp. 248
Indexp. 253
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