Apoptosis and Beyond

The Many Ways Cells Die

James A. Radosevich

• Publisher: Wiley-Blackwell
• Year: 2018
• Print ISBN: 9781119432425
• eBook ISBN: 9781119432432
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Cell Biology
• Index: Biological Sciences

These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death

This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each.

Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death.

• Covers all known processes that dying cells undergo
• Provides extensive coverage of a topic not fully covered before
• Offers chapters written by top researchers in the field
• Provides activities that link and contrast processes to each other

Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.

1
General View of the Cytoplasmic and Nuclear Features of Apoptosis

Humberto De Vitto,¹ Juan P. Valencia,² and James A. Radosevich³

¹Center of Health and Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

²University of Rio de Janeiro, Rio de Janeiro, Brazil

³Department of Oral Medicine and Diagnostic Sciences, University of Illinois at Chicago, Chicago, IL, USA

Abbreviations

AIF	apoptosis-inducing factor
Apaf-1	apoptotic protease activating factor-1
ATP	adenosine triphosphate
BA	bongkrekic acid
Bcl-2	B-cell lymphoma-2
BID	BH3-interacting domain death agonist
bp	base pair
CAD	caspase-activated DNase
c-FLIP	cellular FLICE-inhibitory protein
Chx	cyclohexamide
CsA	cyclosporine A
CTL	cytotoxic T lymphocyte
cyt c	cytochrome c
DISC	death-inducing signal complex
DED	death effector domain
endo D	endonuclease D
endo G	endonuclease G
ER	endoplasmic reticulum
FADD	Fas-associated death-domain protein
FasL	fatty acid synthetase ligand
FasR	fatty acid synthetase receptor
Gzm-A	granzyme-A
Gzm-B	granzyme-B
ICAD	inhibitor of caspase-activated DNase
Kb	kilobase
MEF	mouse embryonic fibroblast
MOMP	mitochondrial outer-membrane permeabilization
NK	natural killer
OMM	outer mitochondrial membrane
PCD	programmed cell death
PFN	Perforin
PT	pore transition
RIP	receptor-interacting protein
ROCK I	Rho effector protein
ROS	reactive oxygen species
SET	stress-response complex
tBID	truncated BID
TNF	tumor necrosis factor
TNFR1	tumor necrosis factor receptor 1
TRADD	TNF receptor-associated death domain
TUNEL	terminal deoxynucleotide tranferase dUTP nick end labeling

1.1 Introduction

The normal development of a cell and the life cycles of the multicellular organism rely on a finely tuned balance between cell survival and death. In a biological context, cells need to grow, divide, and die. In regard to the latter process, cells have developed a very precisely regulated means of programmed cell death (PCD), which contributes to the maintenance of normal cell turnover, leading to reduced impact on tissues, organs, and the organism itself. Some cells have evolved a PCD process called apoptosis. Apoptosis can be simply defined as a set of biochemical cytoplasmic and mitochondrial events that may lead to the execution phase of nuclear events.

A wide array of stress stimuli can trigger the apoptotic process, and the biochemical signal can then be amplified in the cytoplasm and mitochondria by both extrinsic and intrinsic pathways. The convergence of the apoptotic signal is considered the activation of a family of cysteine aspartyl-specific proteases (caspases), composed of 12 proteins strictly involved in the apoptotic cell death process. The dying cells activate the execution pathway that leads to the appearance of blebs and to the “pinching off” of many of them, forming “apoptotic bodies,” which may be rounded and retracted from their own tissue. Subsequently, the immune system cells are able to eliminate the apoptotic bodies through an engulfment cell process. The morphological and biochemical features during the apoptotic process are not fully understood.

At the nuclear level, it is well established that endonucleases and exonucleases may hydrolyze the DNA into small fragments (200 pb) [1]. The nuclear events depend on caspase activation. Caspase 3 is considered the most important protease of the executioner pathway, and is activated by different initiator caspases. For instance, caspase 8 is activated from the death receptor, caspase 9 is involved in the mitochondrial apoptotic process, and caspase 10 is involved in the Perforin/granzyme (PFN/Gzm) pathways. The cleaved caspase 3 cleaves the endonuclease caspase-activated DNase (CAD), degrading the DNA at nucleosomal linkers [2,3], which generates small DNA fragments (∼50–300 kb). The subsequent processing of the DNA by exonucleases and endonucleases leads to the formation of 200 bp fragments. Many organelles, such as the Golgi apparatus, endoplasmic reticulum (ER), lysosomes, and mitochondria, can be recycled or eliminated, depending on the apoptotic stimuli. It is important to note that mitochondria play a pivotal role in apoptosis, since they can release cytochrome c (cyt c) and endonuclease D (endo D), leading to cell death [4,5].

One of the apoptotic pathways is the extrinsic or death-receptor pathway. It depends for its activation on a death domain and a death ligand, such as tumor necrosis factor alpha (TNFα) and tumor necrosis factor receptor 1 (TNFR1). The ligand represents the external death signal, leading to the intracellular signaling of the effector pathway. The main receptors recruit adaptor proteins like Fas-associated death-domain protein (FADD), TNF receptor-associated death domain (TRADD), and receptor-interacting protein (RIP) [6–8], which in turn recruit other molecules such as pro-caspase 8. The dimerization of the death effector domain (DED) leads to the formation of a death-inducing signal complex (DISC), triggering the subsequent process of autocatalysis of pro-caspase 8 to an activated protein (caspase 8) [9]. Caspase 8 activation is considered the main feature that starts the extrinsic pathway, leading to cell death. In many cases, depending on the apoptotic stimuli, the extrinsic pathway can crosstalk with the intrinsic pathway through proteolysis of the BH3-only protein, BH3-interacting domain death agonist (BID), which is what promotes the release of cyt c from the mitochondria into the cytoplasm. In the cytoplasm, cyt c may be assembled with the adaptor protein apoptotic protease activating factor-1 (Apaf-1) and ATP, generating in the cytosol the multimolecular holoenzyme complex called the “apoptosome” (Figure 1.1) [10].

Figure 1.1 Schematic representation of the cytoplasmic and nuclear events of apoptosis. The Perforin/Granzyme pathway, extrinsic pathway, and intrinsic pathway represent the three main pathways of apoptosis. Through a vast array of death signals, all three pathways can be triggered. (A) The Perforin/Granzyme pathway is a unique pathway that partially works in a caspase-independent fashion (granzyme A branch), leading directly to DNA cleavage and cell death. However, the activation of the granzyme B branch can trigger initiator caspase 10, which activates executioner caspase 3. (B) The extrinsic pathway, when activated, can cleave pro-caspase 8 to caspase 8 by FAAD, then activate executioner caspase 3. Caspase 8 plays an important role in the activation of a truncated BID (tBID) protein, leading to the release of mitochondria proteins like cyt c. (C) Upon receiving incoming signals, the intrinsic pathway induces MPTP opening, leading to the release from the mitochondria of proteins such as cyt c, endo G/AIF, and Htra2/Omi. On the cytosol, cyt c forms the apoptosome, which cleaves pro-caspase ...

Table of contents

• Cover
• Title Page
• Copyright
• List of Contributors
• Chapter 1: General View of the Cytoplasmic and Nuclear Features of Apoptosis
• Chapter 2: Mitochondria in Focus: Targeting the Cell-Death Mechanism
• Chapter 3: Microbial Programmed Cell Death
• Chapter 4: Autophagy
• Chapter 5: Cell Injury, Adaptation, and Necrosis
• Chapter 6: Necroptosis
• Chapter 7: Ferroptosis
• Chapter 8: Anoikis Regulation: Complexities, Distinctions, and Cell Differentiation
• Chapter 9: Cornification
• Chapter 10: Excitotoxicity
• Chapter 11: Molecular Mechanisms Regulating Wallerian Degeneration
• Chapter 12: Pyronecrosis
• Chapter 13: Phenoptosis: Programmed Death of an Organism
• Chapter 14: Molecular Mechanisms Underlying Oxytosis
• Chapter 15: Pyroptosis
• Chapter 16: Paraptosis
• Chapter 17: Hematopoiesis and Eryptosis
• Chapter 18: Cyclophilin D-Dependent Necrosis
• Chapter 19: Role of Phospholipases in Cell Death
• Chapter 20: TRIAD (Transcriptional Repression-Induced Atypical Death)
• Chapter 21: Alkylating-Agent Cytotoxicity Associated with O6-Methylguanine
• Chapter 22: Entosis
• Chapter 23: Mitotic Catastrophe
• Chapter 24: NETosis and ETosis: Incompletely Understood Types of Granulocyte Death and their Proposed Adaptive Benefits and Costs
• Chapter 25: Parthanatos: Poly ADP Ribose Polymerase (PARP)-Mediated Cell Death
• Chapter 26: Methuosis: Drinking to Death
• Chapter 27: Oncosis
• Chapter 28: Autoschizis: A Mode of Cell Death of Cancer Cells Induced by a Prooxidant Treatment In Vitro and In Vivo
• Chapter 29: Programmed Death 1 (PD1)-Mediated T-Cell Apoptosis and Cancer Immunotherapy
• Index
• End User License Agreement