Synopses & Reviews
This book attempts to analyze the latest discoveries in sphingolipid biology and how the alteration of their metabolism leads to altered signaling events and to the development of pathobiological disorders, such as cancer, cardiovascular diseases, asthma, diabetes, inflammation and infectious diseases.
Synopsis
This book examines the latest discoveries in sphingolipid biology and how the alteration of their metabolism leads to altered signaling events and to the development of pathobiological disorders, such as cancer, cardiovascular diseases, asthma and diabetes.
About the Author
CHARLES CHALFANT is a tenured Associate Professor of Biochemistry and Molecular Biology at Virginia Commonwealth University-School of Medicine. He is also a Research Career Scientist in the Veterans Administration based at the Hunter Holmes McGuire Veterans Administration Medical Center in Richmond, Virginia. His main research interests lie in lipid signaling, specifically the role of intracellular lipid second messengers (e.g., ceramide-1-phosphate) in regulating eicosanoid synthesis. He also studies the role of oncogenic signaling pathways in regulating the alternative splicing of tumor suppressor genes such as caspase 9. Dr. Chalfant serves on the Editorial Board of The Journal of Lipid Research as well as on several National Panels of Scientific Review including formal membership on the Cancer Molecular Pathobiology Study Section for the National Institutes of Health and the Oncology A Study Section for the Veterans Administration. He received his PhD degree from the University of South Florida-College of Medicine and did his postdoctoral studies at Duke University and the Medical University of South Carolina. MAURIZIO DEL POETA , MD is a tenured Associate Professor of Biochemistry and Molecular Biology, Microbiology and Immunology, Craniofacial Biology, and for the Division of Infectious Diseases at the Medical University of South Carolina, Charleston, South Carolina, USA. He is also the Director of the Graduate Program in Biochemistry and Molecular Biology at MUSC. Main research interests include the study of the role of sphingolipids in fungal pathogenesis and the development of new diagnostic and therapeutic strategies against fungal infections. He received many awards for his research discoveries and teaching. He is also a member of many national and international societies such as the American Society for Clinical Investigation (ASCI), the American Society for Biochemistry and Molecular Biology, and the American Society for Microbiology. Dr. Del Poeta is a Burroughs Wellcome New Investigator in the Pathogenesis of Infectious Diseases.
Table of Contents
1. An Overview of Sphingolipid Metabolism: From Synthesis to BreakdownChristopher R. Gault, Lina M. Obeid and Yusuf A. HannunAbstractSphingolipid Properties in MembranesDe Novo Synthesis in the ERCeramide Transport from the ER to the GolgiSynthesis of Complex SphingolipidsCeramide Kinase and Ceramide'[1'[PhosphateCatabolizing Complex Sphingolipids and Sphingomyelins into CeramideThe Catabolism of Ceramides and the Final Common Breakdown PathwayConclusion2. Sphingolipid TransportLaura Riboni, Paola Giussani and Paola VianiAbstractIntroductionIntramembrane Sphingolipid MovementsIntermembrane Sphingolipid TransportConclusion3. Sphingolipid Analysis by High Performance Liquid Chromatography'[Ta ndem Mas Spectrometry (HPLC'[MS/MS)Jacek Bielawski, Jason S. Pierce, Justin Snider, Barbara Rembiesa, Zdzislaw M. Szulc and Alicja BielawskaAbstractIntroductionSphingolipids: Structure and CompositionLC'[MS Methods for Detection and Analysis of Bioactive SphingolipidsLipidomic ApproachSample PreparationAnalysis of Intact Sphingolipids by Mass SpectrometryMechanism of Electrospray Ionization Mass Spectrometry (ESI/MS)MS Scan ModesSpecific Scan Modes for MS/MS InstrumentationSphingolipid IdentificationHPLC'[MS/MS MethodologyQuantitationSelection of Internal Standards (ISs)Quantitative CalibrationData HandlingAlternative MethodologyConclusion4. Ceramide Synthases: Roles in Cell Physiology and SignalingJohnny Stiban, Rotem Tidhar and Anthony H. FutermanAbstractIntroductionFatty Acid Specificity, Kinetics and Tissue DistributionInhibitorsPosttranslational ModificationsMembrane TopologyWhy Are There So Many Mammalian CerS?Roles of CerS in Signal Transduction and DiseaseConclusion5. Tales and Mysteries of the Enigmatic Sphingomyelin Synthase FamilyJoost C.M. Holthuis and Chiara LubertoAbstractSphingomyelin Biosynthesis: An Historical PerspectiveThe Multigenic Sphingomyelin Synthase (SMS) FamilyCellular Functions of SMS Family MembersConclusion6. Ceramide in Stress ResponseMariana N. Nikolova'[Karakashian and Krassimira A. RozenovaAbstractIntroductionChemical Structure and Biophysical Properties of CeramideChanges in Ceramide Mass During StressMechanisms for Ceramide Generation During StressMechanisms of Ceramide Effects on Cellular FunctionsConclusion7. Animal Models for Studying the Pathophysiology of CeramideToshihiko KawamoriAbstractIntroductionSphingosine Kinase 1/2CeramidasesSphingomyelinases (SMase) and Sphingomyelin Synthases (SMS)S1P LyaseThe Other GEM for Sphingolipid'[Related EnzymesConclusion8. Ceramide 1'[Phosphate in Cell Survival and Inflamatory SignalingAntonio G"mez'[Muoz, Patricia Gangoiti, Mara H. Granado, Lide Arana and Alberto OuroAbstractIntroductionCeramide 1'[Phosphate Synthesis and DegradationCeramide 1'[Phosphate: A Key Regulator of Cell Growth and SurvivalCeramide 1'[Phosphate and the Control of Inflammatory ResponsesCeramide 1'[Phosphate Mediates Macrophage MigrationConclusion9. Ceramide'[1'[Phosphate in Phagocytosis and Calcium HomeostasisVania Hinkovska'[Galcheva and James A. ShaymanAbstractCeramide'[1'[Phosphate in PhagocytosisCeramide'[1'[Phosphate as a Regulator of Calcium HomeostasisConclusion10. Extracellular and Intracellular Actions of Sphingosine'[1'[PhosphateGraham M. Strub, Michael Maceyka, Nitai C. Hait, Sheldon Milstien and Sarah SpiegelAbstractIntroductionSphingolipid MetabolismSphingosine KinasesEvidence for Intracellular Targets of S1PImplications, Future Directions, and Conclusion11. Glucosylceramide in HumansMaria C. Messner and Myles C. CabotAbstractIntroductionGlucosylceramide Synthesis and DegradationMultiple Functions of GlucosylceramideConclusion12. Gangliosides as Regulators of Cell Membrane Organization and FunctionsSandro Sonnino and Alessandro PrinettiAbstractIntroductionSegregation of Membrane Lipids and Detergent'[Resistant Membrane DomainsLipid Membrane Domain FunctionsThe Regulation of Glycosphingolipid Composition of the Plasma Membranes13. Cancer Treatment Strategies Targeting Sphingolipid MetabolismBabak Oskouian and Julie D. SabaAbstractIntroductionSphingolipid MetabolismCeramide Generated via Different Biochemical Routes Can Induce ApoptosisCeramide as a Mediator of Cell Death by Chemopreventive AgentsCeramide Influences Both the Intrinsic and Extrinsic Apoptotic PathwaysSphingosine'[1'[Phosphate as a Counterbalance to CeramideInhibitory Effects of S1P on Apoptotic PathwaysSphingolipids Regulate Key Signaling Pathways that Control Cell FateSphingolipids and AutophagyOther Signaling Pathways Influenced by SphingolipidsCeramide Regulates Cell Cycle ProgressionCeramide and TelomerasesCeramide and S1P in Cancer Stem CellsEffects of S1P on Migration and MetastasisCancer Cells Exhibit Molecular and Genetic Changes in Sphingolipid MetabolismTargeting Sphingolipids for Cancer TherapyS1P Signaling to Protect Normal Tissues from Therapy'[Related CytotoxicityConclusion14. Therapeutic Strategies for Diabetes and Complications: A Role for Sphingolipids?Todd E. Fox and Mark KesterAbstractDiabetes and Insulin ResistanceInsulin Resistance and Altered Sphingolipid MetabolismDiabetic Pancreatic Dysfunction and SphingolipidsDiabetic Cardiovascular Dysfunction and SphingolipidsDiabetic Nephropathy and SphingolipidsDiabetic Retinopathy and SphingolipidsTherapeutics That Target Sphingolipid Metabolism or Sphingolipid Signaling in DiabetesConclusion15. Roles for Sphingolipids in Saccharomyces cerevisiaeRobert C. DicksonAbstractIntroductionSphingolipid Metabolism in S. cerevisiaeMembrane'[Associated Functions and ProcessesSignal Transduction Pathways that Require SphingolipidsLongevity and Cellular AgingRegulation of Sphingolipid BiosynthesisConclusion and Future Developments16. Sphingolipid Signaling in Fungal PathogensRyan Rhome and Maurizio Del PoetaAbstractSphingolipid SynthesisCryptococcus neofomans: Model of Sphingolipid Signaling in FungiSphingolipid Signaling in Other Pathogenic FungiConclusion17. Sphingolipids in Parasitic ProtozoaKai Zhang, James D. Bangs and Stephen M. BeverleyAbstractIntroductionLeishmaniaTrypanosoma brucei (ssp) and Trypanosoma cruziTrypanosomatid Sphingolipid SynthasesPlasmodium falciparumToxoplasma gondiiTrichomonas vaginalis and Giardia lambliaConclusion18. Biosynthesis of Sphingolipids in Plants (and Some of Their Functions)Simone Zñuner, Philipp Ternes and Dirk WarneckeAbstractIntroductionPathway of Plant Sphingolipid BiosynthesisFunctional Characterization of Genes and Enzymes Involved in Plant Sphingolipid Biosynthesis (2004'[2008)Conclusion19. Computational Analysis of Sphingolipid Pathway SystemsEberhard O. Voit, Fernando Alvarez'[Vasquez and Yusuf A. HannunAbstractIntroductionSphingolipid Models and Their Potential UsesConclusionAppendix: Introduction to Tools and Techniques for Ceramide'[Centered ResearchKazuyuki Kitatani and Chiara LubertoAbstractLipid ExtractionIdentification and Quantification of Steady State Levels of CeramideAnalysis of Ceramide MetabolismThe Use of Ceramide AnaloguesPharmacological ToolsGenetic ToolsConclusionINDEX