When cells die : a comprehensive evaluation of apoptosis and programmed cell death /

When Cells Die
CONTENTS
PREFACE
References
CONTRIBUTORS
PART I— THE PHENOMENON OF CELL DEATH
Chapter 1— The Evolutionary Origin and Role of Programmed Cell Death in Single-Celled Organisms: A N...
On the Concomitant Emergence of Programmed Cell Death and Multicellular Organisms: The Paradigm and ...
On the Conserved Nature of Programmed Cell Death in Multicellular Animals
The Paradigm of a Concomitant Emergence of Programmed Cell Death and Multicellular Organisms
From the Explicit Paradigm to the Implicit Paradox
From the Paradox to the Hypothesis
A Paradigm Shift: Programmed Cell Death and Apoptosis in Single-Celled Organisms
On the Choice of an Experimental Model
The Experiments and the Results: Programmed Cell Death and Apoptosis in Trypanosoma Cruzi
The Implications
Other Experimental Findings: Programmed Cell Death in Three Diverging Families of Single-Celled Euka...
The Implications
The Origin of Programmed Cell Death in Single-Celled Organisms: From the Question \\u0027\\u0027When" to the Que...
Limits in Evolutionary Time Traveling: All Contemporaries Are Survivors
A Paradox Concerning the Evolution of Programmed Cell Death: How to Select Genes That Induce a Vanis...
Paradigms, Anomalies, and Retrorecognition Processes
Two Hypotheses for the Evolutionary Origin of Programmed Cell Death: The "Evolutionary Arms Race" Hy...
From "Killing Others" to "Killing Self": The "Evolutionary Arms Race\\u0027\\u0027 Hypothesis
On Toxins, Antidotes, and Interspecies Bacterial Killing
Plasmids, Viruses, and Bacteria: On Toxins, Antidotes, Addiction Modules, and Postsegregational Kill...
From Evolutionary Arms Race to Regulated Self-Destruction: The "Self-Addiction"-Programmed Cell Deat...
How to Decide When to Die: On Quorum Sensing and Cell Differentiation in Bacterial Colonies
A Model for the Resolution of the Paradox of Self-Destruction in Single-celled Organisms: Asymmetric...
From Self-Organization to Self-Destruction: The "Original Sin" Hypothesis
Effectors and Regulators of Programmed Cell Death in Cells from Multicellular Animals
A "Gedanken Experiment" in the First Living Cells: On the Intrinsic Dangers of Gene Products Require...
The Evolution of Genetic Diversification As a Model for the Evolution of Programmed Cell Death
On The Genetic Heterogeneity of "Self": The Synergistic Nature of the "Evolutionary Arms Race" Hypot...
"From Killing Others to Killing Self" and "from Killing Self to Killing Others"
Self-Destruction or Murder: On the Heterogeneous Nature of "Self"
Endosymbiosis As a Stabilization Factor for Programmed Cell Death: The Eukaryote Cell, the Nucleus, ...
The Nucleus and the Mitochondria As Reciprocal Addiction Module
The Use of Bacteria-Related Tools to Control Bacterial-Related Behavior in Eukaryotic Cells: The Con...
On the Nature of Programmed Cell Death Executioners
The Requirement for Mitochondria in the Execution of Single-Celled Eukaryote Programmed Cell Death
Programmed Cell Death in Plants
The Nature of Executioners
\\u0027\\u0027Death From Within" and "Death From Without": Towards a New View on the Role of Death in the Proces...
Genetic Mutation and Natural Selection: The Phenotype As the Vehicle or the Grave of the Genome
Cell Differentiation in Single-Celled Organisms: Several Vehicles and Graves for a Given Genome
Programmed Cell Death in Single-Celled Organisms: Using the Grave to Optimize the Vehicle
Addiction As a Point of No Return: Programmed Cell Death As an Evolutionary Switch between Chance an...
Acknowledgments
References
Chapter 2— The Reactions of Cells to Lethal Injury: Oncosis and Necrosis--The Role of Calcium
Introduction
Reactions of Cells to Injury
Prelethal Changes in Cells
Oncosis
Apoptosis
Necrosis
Concept of Programmed Cell Death
Differences between Oncosis and Apoptosis
Oncosis--Stages
Stage 2
Morphology
Biochemistry/Function
Stage 3
Morphology
Biochemistry/Function
Energy Metabolism
Ion Regulation
Signalling/Nuclear Function
Stage 4
Morphology
Biochemistry/Function
Necrosis
Description
Stage 5
Morphology
Biochemistry/Function
Stage 6
Stage 7
Mechanisms of Oncosis Leading to Cell Death
Altered Cell Volume Regulation
Altered [Ca2+]i Regulation
Altered Energy Metabolism
Protein Denaturation
Activation of Hydrolytic Enzymes
Proteases
Cysteine Proteases/ICE Family
Calpains
Lysosomal Proteases
Nucleases
Phospholipases (see Zakeri, Chapter 3, Benitez, Chapter 17, This Volume)
Signalling Pathways
Immediate-Early Genes (See Osborne, Chapter 8, Papermarker, Chapter 12, Birge et al, Chapter 13, Til...
Activation of p53
Stress Genes
Cytoskeleton
Actin
Tubulin
Intermediate Filaments
Agents and Gene Products That Protect against Cell Death
Bcl-2 (See Birge et al, Chapter 13, Tilly, Chapter 16, Benitez, Chapter 17, Cryns and Yuan, Chapter ...
Low pH
Hypothermia
Phospholipase Inhibitors
Protease Inhibitors
Nuclease Inhibitors
Amino Acids
Modification of [Ca2+]i
Hypothesis
Conclusion
Acknowledgments
References
Chapter 3— The Study of Cell Death by the Use of Cellular and Developmental Models
Characterization of Cell Death
Type I Cell Death (Apoptosis)
Type II (Lysosomal) Cell Death
Cell Death in Development
Cell Death in Embryogenesis
Cell Death in Developing Limbs
Cell Death in Metamorphosing Insect Tissue
Identification of Cell Death
Morphological Analysis
Engulfment of Dead Cells
Destruction of the Dead Cell
DNA Fragmentation of the Apoptotic Cell
Metabolic Changes in Dying Cells
Addressing the Mechanisms of Cell Death
Comparison of Normal and Abnormal Cell Death in the Limb
Analysis of Cell Death Related Genes
Extracellular Signals Controlling Cell Death
Signal Transduction Pathways in Cell Death
Acknowledgments
References
Chapter 4— Genetic Approaches to Programmed Cell Death in C. elegans
Introduction
Identity and Origin of Cells Undergoing Programmed Cell Death During C. Elegans Development
Identification and Quantification of Programmed Cell Death in C. elegans
Mutants Define Four Distinct Steps in the Apoptotic Pathway
Three Genes, ced-3, ced-4, and ced-9, Define a Genetic Pathway Needed for all Programmed Cell Deaths...
ced-3 and ced-9 are Functionally Conserved Throughout Evolution
CED-3, CED-4, and CED-9 Are Part of a Molecular Framework Regulating Programmed Cell Death
The Regulation of Programmed Cell Death in Specific Cell Types
Genes Required for the Engulfment of Dying Cells
Potential Functions of Programmed Cell Death During the Development of C. elegans
Conclusion
Acknowledgments
References
Chapter 5— Cell Death in Plants
Introduction
Occurrence of Programmed Cell Death in Plants
Developmental pcd in Plants: From Reproduction to Senescence
Pcd During Reproduction in Plants
Floral Organ Abortion
Megaspore Abortion
Tapetum Degeneration
Pcd Preventing Self-Pollination
Pcd During Embryogenesis and Germination in Plants
Pcd of the Embryo Suspensor
Cell Death in Storage Tissue
Cell Death in Maturing Plant Organs
Formation of Tracheary Elements
Death of Root Cap Cells
Morphogenesis of Leaf Structure
Cell Death at the Stem
Cell Death During Senescence
Environmental pcd in Plants: Biotic and Abiotic
Activation of pcd in Response to Abiotic Stress
Pcd of Hair Cells
Autolysis of the Aerenchyma
Activation of pcd in Response to Pathogens (Biotic Stress)
PCD during the Differentiation of Tracheary Elements
Pathogen-Induced Programmed Cell Death in Plants
Plant-Pathogen Interactions and the Hypersensitive Response
The Genetics of the Hypersensitive Response
Biochemistry, Morphology, and Detection of Pathogen-Induced pcd
Detection of pcd in Plants
Cleavage of DNA and Activation of Proteases
Morphology of pcd in Plants
Signal Transduction during Pathogen-Induced Cell Death
What Is the Role of pcd in Plant Protection?
Summary
Acknowledgments
References
PART II— THEMES AND APPROACHES TO CELL DEATH
Chapter 6— The Cutting Edge: Caspases in Apoptosis and Disease
Introduction
Multiple Mammalian Homologues of CED-3
Role of Caspases in Apoptosis
Overexpression of Caspases Induces PCD
Caspases Are Activated during PCD
Inhibitors of Caspases Prevent PCD
Viral Inhibitors
Peptide Inhibitors
Dominant Negative and Antisense Inhibitors
Activation of a Caspase Proteolytic Cascade During PCD
Granzyme B Mediates Ctl-Induced Apoptosis of Target Cells by Activating Caspases
Apoptotic Substrates of Caspases
Role of Caspases in Disease
Acknowledgments
References
Chapter 7— Endonuclease Activities and Apoptosis
Introduction
Endonucleases Implicated in Apoptosis
Association of an Endonuclease with Cell Death (Research from 1970 to 1990)
Role of Calcium Ions in DNA Fragmentation
Ca2+/Mg2+-Dependent Endonucleases
Changes in Intracellular Ca2+ Levels during Apoptosis
Acidification and the Role of Acidic Endonucleases
Other Endonucleases Implicated in Apoptosis
Nuc18
Endo-Exonuclease
Changes in Endonuclease Activity during Development and Differentiation
DNA Sequence Requirements for Fragmentation
New Aspects of the Mechanism of DNA Fragmentation
Generation of High-Molecular-Weight DNA Fragments
Chromatin Structure and HMW DNA Fragmentation
Formation of Single-Strand Breaks in Apoptotic DNA
Matrix Enzymes
Initial Morphological Changes to the Nucleus
Site-Specific Proteolysis
Summary and Future Directions
References
PART III— CELL DEATH WHEN MITOSIS IS HIGH AND EVANESCENCE IS DESIRABLE
Chapter 8— Apoptotic Signaling Pathways in Lymphocytes
Introduction
Cell Death in the Thymus
Genetic Regulation of Apoptosis in the Thymus
Cell Death in Peripheral T Cells
Fas and Fas Ligand and the Regulation of Apoptosis in T Lymphocytes
CTL-Induced Target Cell Death
Survival Signals in Lymphocytes
Other Molecular Mediators of Lymphoid Cell Death
Proteases and Cell Death in the Immune System
Cell Death and Disease in the Immune System
Conclusions and Summary
Acknowledgments
References
Chapter 9— Regulation of Immune Responses by Immune Directed Cell Death
An Introduction to the Immune System
Cell Death in the Developing Immune System
The Role of Major Histocompatibility Encoded Molecules in Cell Death
Cd8+ T-Cell-Mediated Killing of Infected Target Cells
Cell Death in Peripheral Immune Function
Regulation of Immune-Directed Cell Death
Natural Killer-Mediated Cell Death
gd T Cells And CD4+ T-Cell Deletion
References
Chapter 10— Apoptosis in Autoimmunity
Apoptosis in the Immune System
Autoimmunity Resulting from Genetics Defects in the Apoptotic Machinery
Apoptosis as a Source of Autoantigens
Autoimmunity due to Apoptosis of the Innocent Bystander
Superantigens
References
Chapter 11— AIDS And Cell Death
Introduction
The Immune System
HIV Infection
The HIV Genome
HIV Replication
The Clinical History of HIV Infection
HIV Pathogenesis
Apoptosis in HIV Infection
Definition of Apoptosis
Apoptosis Assays
Apoptosis in HIV-Infected Individuals and in Models of HIV Disease
Apoptosis of Uninfected CD4+ T Cells
Mechanisms of Apoptosis in HIV Infection
Fas-Fas-L Interactions
Regulation of Fas/Fas-L Expression by HIV-Encoded Proteins
The CD4-gp120 Interaction
Signaling for Death
Apoptosis of Thymocytes in HIV Disease
Protection of HIV-Infected Cells from Apoptosis
Down-Regulation of CD4
Inhibition of Apoptosis by HIV-Encoded Proteins
Inhibition of Cellular Activation by HIV-Encoded Proteins
How Do Infected Cells Die?
CD8+ T Cells in HIV Infection
Summary and Future Directions
References
PART IV— CELL DEATH IN LONG-LIVED CELLS
Chapter 12— Apoptosis of Tissues of the Eye During Development and Disease
Introduction
The Development of the Eye and the Differentiation of the Lens
Apoptosis of the Retina during Development
Apoptosis of the Human Retina in Disease
Photoreceptor Cell Structure and Visual Cell Excitation
Mutations Causing Retinal Degenerations in Humans Have Parallels in Mice
Experimental Studies of Retinal Degenerations
Perturbation of the Cell Cycle by Viral Oncoproteins Causes Retinal Apoptosis and the Development of...
The Role of the bcl-2 Family in Retinal Apoptosis
Some Soluble Factors Ameliorate Retinal Degenerations in Rats and Mice
Studies in Drosophila Melanogaster Offer Hope of a Cure
Apoptosis of the Lens Is Induced by Experimental Dysregulation of the Cell Cycle
The Development of the Normal Lens and the Effect of Loss of Function of Rb and p53 Genes
Perturbation of Cell Cycle Genes by Using Viral Oncoproteins in Transgenic Mice and Lens-Specific Pr...
Extraretinal Expression of IRBP Transgenes in the Lens
Studies of Lens Development in Chimeric Mice
The Need to Evaluate the Eye As an Entire Organ
Conclusions and Anticipation of New Areas of Research
References
Chapter 13— Signal Transduction and Neuronal Cell Death during Development and Disease
Neurotrophin Receptors
Role of Neurotrophins and Neurotrophin Receptors during Neuronal Differentiation and Survival
Signal Transduction by the Trk Tyrosine Kinase
TrkA Effector Pathways Involved in Neuronal Survival
p21ras Activation and Defective Cell Cycle
Trk Isoforms and Modulation of Receptor Function
The P75 Neurotrophin Receptor
Role of p75 in Neurotrophin Internalization and Trk-Mediated Survival
Role of p75 in Ligand-Dependent Apoptosis
Signal Transduction by the p75 NGF Receptor: Relation to TNFR1 and Fas
Apoptotic and Anti-Apoptotic Genes in Neural Cells
ICE Proteases in Neuronal Apoptosis
Bcl-2 Family Proteins and Neuronal Survival
Bcl-2 and the Mitochondria
Role of Reactive Oxygen Species (Ros) in Neuronal Cell Death
Signal Transduction by ROS
Role of ROS in Neurodegenerative Disease
Summary and Future Prospectus
Acknowledgments
References
Chapter 14— Cell Death in Alzheimer\\u0027s Disease
Introduction
b-Amyloid Initiates Apoptosis in Cultured Primary Neurons
Many Inducers of Apoptosis Accumulate in the AD Brain
Genetic Risk Factors for Apoptosis: The Presenilin Genes May Place Neurons at Increased Risk for Ap...
Apoptosis in the AD Brain
Activation-Induced Cell Death May Be a Common Theme in Neuronal Apoptosis
Prototypical Apoptosis Pathways: Staurosporine Versus Activation of the Fas/Apo-1 Receptor
DNA Damage and Activation Versus Inhibition of the Degeneration Program
Anti-Apoptotic Mechanisms Are Induced in the AD Brain
Glial Cells and Vascular Smooth Muscle Cells Also Show Indications of Apoptosis
Conclusions
References
Chapter 15— Regulation of Apoptosis by Cellular Interactions with the Extracellular Matrix
Introduction
The Biological Significance of Regulating Cell Death by Cell-ECM Interactions
ECM Receptors and Their Role in Regulating Apoptosis
ECM Binding, Cell Shape, Cell Deformation, and the Regulation of Apoptosis
Identification of Cell-ECM Interactions As a Regulator of Apoptosis in Vivo
Summary
References
PART V— THE CLINICAL RELEVANCE OF APOPTOSIS
Chapter 16— Cell Death and Species Propagation: Molecular and Genetic Aspects of Apoptosis in the Ve...
Introduction
Endocrine Regulation of Apoptosis in the Ovary
General Concepts
Endocrine Control of Ovarian Somatic Cell Death
Hormonal Regulation of Apoptosis in Germ Cells
Intracellular Events Involved in Apoptosis in the Ovary
General Comments
The bcl-2 Gene Family
The p53 Tumor Suppressor Protein
The CASP Gene Family
Early Signaling Pathways
Apoptosis and the Ovary: Implications and Future Directions
Acknowledgments
References
Chapter 17— Assessment of Apoptosis in Tumor Growth: Importance in Clinical Oncology and Cancer Ther...
Introduction
Multistep Carcinogenesis and Programmed Cell Death
Cell Death: A Major Factor in Loss of Tissue Homeostasis in Cancer
Cell Replication, Differentiation and Apoptosis in Grading Malignant Neoplasias
Cell Death: Important but Difficult to Assess in Neoplasia
Potential for the Evaluation of Cell Death As a Prognostic Indicator in Human Malignant Neoplasias
DNA-Based Techniques
Currently Available and Needed Techniques to Estimate Apoptosis
Genetic Deregulation of Apoptosis in Malignant Tumors
Genes Involved in Growth, Cell Cycle, or Unknown Function Whose Mutations Correlate with Malignancy
Tumor Suppressor Gene p53: Cell Cycle Arrest, Apoptosis, or Both?
The Inhibitor Gene bcl-2 a Potential Prognosticator?
Myc, a Putative Proapoptotic Protein
The Fas/APO-1-Mediated Apoptosis and Its Loss in Tumors
Signaling and Effectors May Be Detected As Indicators of Cell Death
ICE-Like Proteases and Ceramide Generation
Other Factors and the Common Pathway of Apoptosis
Current Assessment of Cell Death in Malignant Neoplasias
Apoptosis in Prostatic Adenocarcinoma
Leukemias and Lymphomas The bcl-2 Connection
Testicular Tumors
Induction of Apoptosis in the Treatment of Cancer
References
INDEX
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