Phospholipases in Physiology and Pathology

Phospholipases in Physiology and Pathology

1st Edition - August 1, 2023

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  • Editor: Sajal Chakraborti
  • Hardcover ISBN: 9780323956871

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Phospholipases in Physiology and Pathology presents a comprehensive overview on the physiology and pathology of phospholipases. This five-volume set considers the biochemical and molecular mechanisms of normal and abnormal cell function upon dysregulation of phospholipases in different diseases. Additionally, the book discusses the use of phospholipases and their metabolites and downstream signaling components as therapeutic targets for establishing prevention strategies. Volumes cover signal transduction mechanisms, implications in cancer, infectious diseases, neural diseases, cardiovascular diseases and other diseases, implications in inflammation, apoptosis, gene expression and non-coding RNAs, the role of natural and synthetic compounds, and stem cell therapies, nanotechnology-based therapies, and more. Together, these volumes give researchers critical insight on the mechanistic and therapeutic aspects of phospholipases.

Key Features

  • Discusses the biochemical and molecular mechanisms of normal and abnormal cell function in different disease processes
  • Covers a wide range of basic and translational research appropriate for scientists engaged in studying the regulation of phospholipases from interdisciplinary perspectives
  • Features state-of-the-art chapter contributions from international leaders in the field


Researchers in Cell Biology, Molecular Biology, Biochemistry, Medicinal Chemistry, and related Biomedical fields, Clinicians and students

Table of Contents

  • Volume-1-Modulation of Signal Transduction Mechanisms, Inflammation and Immune Response
    General Aspects
    1. Role of G proteins in regulating PI3K-PLD-PKCz for stimulation of NADPH oxidase derived O2.- in pulmonary vasculature.
    2. Role of Phospholipase A2 in Cancer Development and Progression.
    3. Phospholipase A2 isoforms in health and disease.
    4. Type IIA Secreted Phospholipase A2 in Host Defense against Bacterial Infections.
    5. In vitro antifungal activities of inhibitors of phospholipases from the fungal pathogen Cryptococcus neoformans.
    6. Antimicrobial proteins from snake venoms: direct bacterial damage and activation of innate immunity against Staphylococcus aureus skin infection.
    7. Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane.
    8. Bacteria induce prolonged PMN survival via a phosphatidylcholine-specific phospholipase C- and protein kinase C-dependent mechanism.
    9. Antibacterial effects of human group IIA and group XIIA phospholipase A2 against Helicobacter pylori in vitro.
    10. Phospholipase D and phosphatidic acid in plant immunity.
    11. Role of proteases in Phospholipase A2 activation.
    12. Crystal structure of plant PLDα1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase
    13. Phospholipases: at the crossroads of the immune system and the pathogenesis of HIV-1 infection.
    A. Modulation of Signal Transduction Mechanisms
    14. The Phosphoinositide Signal Transduction Pathway in the Pathogenesis of Alzheimer's Disease.
    15. Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes.
    16. Signal transduction in pancreatic beta-cells: regulation of insulin secretion by information flow in the phospholipase C/protein kinase C pathway.
    17. Calcium-independent phospholipases in the heart: mediators of cellular signaling, bioenergetics, and ischemia-induced electrophysiologic dysfunction.
    18. Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia.
    19. Disruption of PLC-beta 1-mediated signal transduction in mutant mice causes age-dependent hippocampal mossy fiber sprouting and neurodegeneration.
    20. Activation of PLCγ/AKT/IκBα/p65 signaling increases inflammation in mast cells to promote growth of cutaneous neurofibroma.
    21. Nuclear Inositide Signaling Via Phospholipase C.
    22. Dysfunction of phospholipase Cγ in immune disorders and cancer.
    23. Nuclear phosphoinositide specific phospholipase C (PI-PLC)-beta 1: a central intermediary in nuclear lipid-dependent signal transduction.
    24. Phospholipases A2 and neural membrane dynamics: implications for Alzheimer's disease.
    25. Phospholipase A2 and its molecular mechanism after spinal cord injury.
    26. Phospholipase C zeta (PLCζ) and male infertility: Clinical update and topical developments.
    27. Functions and pathophysiological roles of phospholipase D in the brain
    28. Integrating cytosolic phospholipase A₂ with oxidative/nitrosative signaling pathways in neurons: a novel therapeutic strategy for AD.
    29. PLCγ1-PKCε-IP3 R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells.
    B. Modulation of Inflammation and Immune Response
    30. Phospholipase Cγ in Toll-like receptor-mediated inflammation and innate immunity.
    31. Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression.
    32. Secreted Phospholipase A2 Group X Acts as an Adjuvant for Type 2 Inflammation, Leading to an Allergen-Specific Immune Response in the Lung.
    33. iPLA2β and its role in male fertility, neurological disorders, metabolic disorders, and inflammation.
    34. Phospholipases: at the crossroads of the immune system and the pathogenesis of HIV-1 infection.
    35. COVID-19 and arachidonic acid pathway.
    36. Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2 and COX inhibitors abolish long-term memory failure induced by systemic immune challenges.
    37. Roles of secreted phospholipase A2 group IIA in inflammation and host defense.
    38. The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response.
    39. The Roles of the Secreted Phospholipase A2 Gene Family in Immunology.
    40. Cytosolic phospholipase A2-alpha is necessary for the innate immune response to pulmonary infection.
    41. Phospholipase D1 plays a key role in TNF-alpha-mediated inflammation in lung.

    Volume-II-Modulation of Gene Expression, NonCoding RNAs and Apoptosis
    A. Modulation of Gene Expression
    1. Differential phospholipase gene expression by Candida albicans in artificial media and cultured human oral epithelium.
    2. Expression of phospholipases A2 and C in human corneal epithelial cells.
    3. Changes in group II phospholipase A2 gene expression in rat heart during sepsis.
    4. Secreted phospholipases A₂ are differentially expressed and epigenetically silenced in human breast cancer cells.
    5. Gene expression of group II phospholipase A2 in intestine in Crohn's disease.
    6. Phospholipase A2 and cyclooxygenase gene expression in human preimplantation embryos.
    7. Heterologous expression of lipoprotein-associated phospholipase A2 in different expression systems.
    8. Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-alpha and IFN-gamma.
    9. Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants.
    10. Lypopolysaccharide downregulates the expression of selected phospholipase C genes in cultured endothelial cells.
    B. Modulation of Apoptosis and Necrosis
    11. Corticotropin-releasing hormone receptors mediate apoptosis via cytosolic calcium-dependent phospholipase A₂ and migration in prostate cancer cell RM-1.
    12. Phospholipase D1 Ameliorates Apoptosis in Chronic Renal Toxicity Caused by Low-Dose Cadmium Exposure.
    13. Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features.
    14. Therapeutic inhibition of phospholipase D1 suppresses hepatocellular carcinoma.
    15. A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis.
    16. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells
    17. Group III secreted phospholipase A2 causes apoptosis in rat primary cortical neuronal cultures.
    18. Cytosolic phospholipase A2 activation correlates with inflammation and consequently estrogen-dependent breast cancer cell growth.
    19. TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic phospholipase A2 and oxidant-dependent mechanisms.
    C. Implications of Natural and Synthetic Compounds
    20. Marine natural products targeting phospholipases A2. Marc Diederich.
    21. Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings.
    22. Structural Insight into Binding Mode of 9-Hydroxy Aristolochic Acid, Diclofenac and Indomethacin to PLA2.
    23. 2-Oxoamides based on dipeptides as selective calcium-independent phospholipase A2 inhibitors.
    24. Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920).
    25. PLCδ1 activating protein rescues ischemia-reperfused heart by the regulation of calcium homeostasis.
    26. Disrupting a phospholipase A2 gene by the oleaginous yeast Yarrowia lipolytica>
    27. Mechanism of inhibition of human secretory phospholipase A2 by flavonoids.
    28. Inhibition of Cytosolic Phospholipase A2α (cPLA2α) by Medicinal Plants in Relation to Their Phenolic Content.
    D. Nanotechnology Based Therapy
    29. Secretory phospholipase A2 responsive liposomes exhibit a potent anti-neoplastic effect in vitro, but induce unforeseen severe toxicity in vivo.
    30. Nanoliposomal delivery of cytosolic phospholipase A2 inhibitor arachidonyl trimethyl ketone for melanoma treatment..
    31. Phospholipid-graphene nanoassembly as a fluorescence biosensor for sensitive detection of phospholipase D activity.
    32. Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78.
    33. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals.

    Volume III-Therapeutic Aspects
    A. Epigenetic Tools and Gene Therapy
    1. Emerging role of microRNAs in lipid metabolism. Li Wang.
    2. Long non‑coding RNA SLNCR1 regulates non‑small cell lung cancer migration, invasion and stemness through interactions with secretory phospholipase A2.
    3. Neuroscience. Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction.
    4. MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma. Zhaohui Huang.
    5. Down-regulation of Phospholipase D Stimulates Death of Lung Cancer Cells Involving Up-regulation of the Long ncRNA ANRIL.
    6. How miRs and mRNA deadenylases could post-transcriptionally regulate expression of tumor-promoting protein PLD.
    7. MicroRNA-145 performs as a tumor suppressor in human esophageal squamous cell carcinoma by targeting phospholipase C epsilon.
    8. Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a.
    9. MiR-543 Promotes Migration, Invasion and Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Targeting Phospholipase A2 Group IVA.
    10. MiR-328 suppresses the survival of esophageal cancer cells by targeting PLCE1.
    11. Promotion of cell autophagy and apoptosis in cervical cancer by inhibition of long noncoding RNA LINC00511 via transcription factor RXRA-regulated PLD1.
    12. Long noncoding RNA SLNCR1 regulates nonsmall cell lung cancer migration, invasion and stemness through interactions with secretory phospholipase A2.
    13. MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma.
    14. Nuclear phospholipase C β1 signaling, epigenetics and treatments in MDS
    B. Stem Cell Therapy
    15. cPLA2α reversibly regulates different subsets of cancer stem cells transformation in cervical cancer.
    16. Requirement for PLCγ2 in IL-3 and GM-CSF-stimulated MEK/ERK phosphorylation in murine and human hematopoietic stem/progenitor cells.
    17. Phospholipase C and protein kinase C involvement in mouse embryonic stem-cell proliferation and apoptosis.
    18. Arachidonic acid potentiates hypoxia-induced VEGF expression in mouse embryonic stem cells: involvement of Notch, Wnt, and HIF-1alpha.
    19. Cooperation of phosphatidylcholine-specific phospholipase C and basic fibroblast growth factor in the neural differentiation of mesenchymal stem cells in vitro.
    20. Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells.
    21. Role of glycosylphosphatidylinositol-specific phospholipase D in the homing of umbilical cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic stem/progenitor cells.
    22. The Involvment of Hematopoietic-Specific PLC -β2 in Homing and Engraftment of Hematopoietic Stem/Progenitor Cells.
    23. Cancer stem cell phenotype is supported by secretory phospholipase A2 in human lung cancer cells.
    24. Secreted Phospholipases A2 Are Intestinal Stem Cell Niche Factors with Distinct Roles in Homeostasis, Inflammation, and Cancer.
    25. cPLA2α reversibly regulates different subsets of cancer stem cells transformation in cervical cancer.
    C. Bioinformatics and System biology Approach
    26. Phospholipase A2 catalysis and lipid mediator lipidomics.
    27. Combined targeted Omic and Functional Assays Identify Phospholipases A₂ that Regulate Docking/Priming in Calcium-Triggered Exocytosis.
    28. Modeling studies on phospholipase A2-inhibitor complexes.
    29. In silico identification of viper phospholipaseA2 inhibitors: validation by in vitro, in vivo studies.
    30. Exploring calcium ion-dependent effect on the intermolecular interaction between human secreted phospholipase A2 and its peptide inhibitors in coronary artery disease.
    31. Integrated mRNA-Seq and miRNA-Seq analysis of PLCγ2-overexpressing hepatocarcinoma cells and identification of the associated miRNA-mRNA network.
    32. Experimental and bioinformatic analysis of cultured Bovine Endometrial Cells (BEND) responding to interferon tau (IFNT).
    33. In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes.
    34. Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes.
    35. Computational biology analysis of platelet signaling reveals roles of feedbacks through phospholipase C and inositol 1,4,5-trisphosphate 3-kinase in controlling amplitude and duration of calcium oscillations.
    36. Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains.
    37. Molecular cloning and characterization in silico of phospholipase A2 transcript isolated from Lachesis muta peruvian snake venom.
    38. In silico investigation of the molecular effects caused by R123H variant in secretory phospholipase A2-IIA associated with ARDS.
    39. Meta-analysis of phospholipase C epsilon 1 polymorphism and cancer risk.
    40. Substrate recognition of PLCγ1 via a specific docking surface on Itk

Product details

  • No. of pages: 1050
  • Language: English
  • Copyright: © Academic Press 2023
  • Published: August 1, 2023
  • Imprint: Academic Press
  • Hardcover ISBN: 9780323956871

About the Editor

Sajal Chakraborti

Dr. Sajal Chakraborti, PhD, DSc is a Professor at the Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India. He did post-doctoral research at the Johns Hopkins Medical Institution, Baltimore; New York Medical College, New York; the University of Utah Health Sciences Center, Salt Lake City, Utah; and the University of Florida, Gainesville, Florida. He has over 35 years teaching and independent research experience in Biochemistry, Molecular Physiology and Cell Biology. He has published over 110 original research articles, 25 review articles and book chapters, and also edited twelve books published by Springer.

Affiliations and Expertise

Professor, Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, India

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