Special Issue "Apoptosis"

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A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 January 2013)

Special Issue Editor

Guest Editor
Dr. Vladimir V. Didenko (Website)

Departments of Neurosurgery and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Phone: +713 794 7572
Fax: +713 794 7095
Interests: neural cell injury and programmed cell death; mechanisms of age-related neural cell death; methods to detect and control programmed cell death in vivo; development and application of nucleic acid-based nanoprobes and molecular machines

Special Issue Information

Dear Colleagues,

Cellular suicide is a fundamental property of animal cells from worms to humans and is essential for the life of an organism. Every second at least one million cells die by apoptosis in the human body. These deaths play roles in a multitude of processes including embryogenesis, development, defense against cancer and infections, self-tolerance in the immune system, etc.

Since the inception of the term in 1972 by Kerr, Wyllie, and Currie, the field of apoptosis has witnessed an outburst of findings and had several paradigm shifts. Studies have revealed the origins of apoptotic machinery going back over a billion years and have uncovered a variety of ways which cells have developed to activate and suppress the apoptotic program.

As the field expanded further, the very concept of apoptotic cell elimination changed. Today apoptosis is no longer viewed as an individual cellular event, but includes the externally-controlled elimination of apoptotic cells by phagocytes in the waste-management phase. At present apoptosis enjoys a celebrity status in cell biology. As the number of publications in the field skyrockets, it is essential to maintain high visibility of individual research. This is the compelling advantage of Open Access journals, such as Cells. This special issue of Cells is dedicated to Apoptosis. We welcome contributions about its mechanisms, role in normal and pathological processes and new techniques for its detection and analysis.  Reviews as well as original papers are invited.

Dr. Vladimir V. Didenko
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • apoptosis
  • programmed cell death
  • caspases
  • cytochrome c
  • death receptors
  • mitochondria-mediated pathway
  • DNA damage
  • necrosis
  • apoptotic cell clearance
  • apoptotic nucleases

Published Papers (15 papers)

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Research

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Open AccessArticle Monte Carlo Study Elucidates the Type 1/Type 2 Choice in Apoptotic Death Signaling in Healthy and Cancer Cells
Cells 2013, 2(2), 361-392; doi:10.3390/cells2020361
Received: 13 March 2013 / Revised: 10 May 2013 / Accepted: 14 May 2013 / Published: 30 May 2013
Cited by 2 | PDF Full-text (1771 KB) | HTML Full-text | XML Full-text
Abstract
Apoptotic cell death is coordinated through two distinct (type 1 and type 2) intracellular signaling pathways. How the type 1/type 2 choice is made remains a central problem in the biology of apoptosis and has implications for apoptosis related diseases and therapy. [...] Read more.
Apoptotic cell death is coordinated through two distinct (type 1 and type 2) intracellular signaling pathways. How the type 1/type 2 choice is made remains a central problem in the biology of apoptosis and has implications for apoptosis related diseases and therapy. We study the problem of type 1/type 2 choice in silico utilizing a kinetic Monte Carlo model of cell death signaling. Our results show that the type 1/type 2 choice is linked to deterministic versus stochastic cell death activation, elucidating a unique regulatory control of the apoptotic pathways. Consistent with previous findings, our results indicate that caspase 8 activation level is a key regulator of the choice between deterministic type 1 and stochastic type 2 pathways, irrespective of cell types. Expression levels of signaling molecules downstream also regulate the type 1/type 2 choice. A simplified model of DISC clustering elucidates the mechanism of increased active caspase 8 generation and type 1 activation in cancer cells having increased sensitivity to death receptor activation. We demonstrate that rapid deterministic activation of the type 1 pathway can selectively target such cancer cells, especially if XIAP is also inhibited; while inherent cell-to-cell variability would allow normal cells stay protected. Full article
(This article belongs to the Special Issue Apoptosis)
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Open AccessArticle Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation
Cells 2012, 1(4), 1156-1167; doi:10.3390/cells1041156
Received: 14 November 2012 / Revised: 24 November 2012 / Accepted: 27 November 2012 / Published: 5 December 2012
Cited by 3 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text
Abstract
Persistent cell shrinkage is a major hallmark of apoptotic cell death. The early-phase shrinkage, which starts within 30−120 min after apoptotic stimulation and is called apoptotic volume decrease (AVD), is known to be accomplished by activation of K+ channels and volume-sensitive [...] Read more.
Persistent cell shrinkage is a major hallmark of apoptotic cell death. The early-phase shrinkage, which starts within 30−120 min after apoptotic stimulation and is called apoptotic volume decrease (AVD), is known to be accomplished by activation of K+ channels and volume-sensitive outwardly rectifying (VSOR) Cl channels in a manner independent of caspase-3 activation. However, it is controversial whether AVD depends on apoptotic dysfunction of mitochondria and activation of initiator caspases. Here, we observed that AVD is induced not only by a mitochondrial apoptosis inducer, staurosporine (STS), in mouse B lymphoma WEHI-231 cells, but also by ligation of the death receptor Fas in human B lymphoblastoid SKW6.4 cells, which undergo Fas-mediated apoptosis without involving mitochondria. Overexpression of Bcl-2 failed to inhibit the STS-induced AVD in WEHI-231 cells. These results indicate that AVD does not require the mitochondrial pathway of apoptosis. In human epithelial HeLa cells stimulated with anti-Fas antibody or STS, the AVD induction was found to precede activation of caspase-8 and caspase-9 and to be resistant to pan-caspase blockers. Thus, it is concluded that the AVD induction is an early event independent of the mitochondrial apoptotic signaling pathway and initiator caspase activation. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessArticle The Anti-Apoptotic Role of Neuroglobin
Cells 2012, 1(4), 1133-1155; doi:10.3390/cells1041133
Received: 29 October 2012 / Revised: 15 November 2012 / Accepted: 21 November 2012 / Published: 23 November 2012
Cited by 6 | PDF Full-text (1163 KB) | HTML Full-text | XML Full-text
Abstract
The small heme-protein neuroglobin is expressed at high concentrations in certain brain neurons and in the rod cells of the retina. This paper reviews the many studies which have recently identified a protective role for neuroglobin, in a wide range of situations [...] Read more.
The small heme-protein neuroglobin is expressed at high concentrations in certain brain neurons and in the rod cells of the retina. This paper reviews the many studies which have recently identified a protective role for neuroglobin, in a wide range of situations involving apoptotic cell death. The origins of this protective mechanism are discussed in terms of both experimental results and computational modeling of the intrinsic pathway of apoptosis, which shows that neuroglobin can intervene in this process by a reaction with released mitochondrial cytochrome c. An integrated model, based on the various molecular actions of both neuroglobin and cytochrome c, is developed, which accounts for the cellular distribution of neuroglobin. Full article
(This article belongs to the Special Issue Apoptosis)
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Review

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Open AccessReview Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia
Cells 2014, 3(1), 36-52; doi:10.3390/cells3010036
Received: 5 December 2013 / Revised: 25 December 2013 / Accepted: 25 December 2013 / Published: 8 January 2014
Cited by 4 | PDF Full-text (3826 KB) | HTML Full-text | XML Full-text
Abstract
Prematurely born infants commonly suffer respiratory dysfunction due to the immature state of their lungs. As a result, clinicians often administer glucocorticoid (GC) therapy to accelerate lung maturation and reduce inflammation. Unfortunately, several studies have found GC therapy can also produce neuromotor/cognitive [...] Read more.
Prematurely born infants commonly suffer respiratory dysfunction due to the immature state of their lungs. As a result, clinicians often administer glucocorticoid (GC) therapy to accelerate lung maturation and reduce inflammation. Unfortunately, several studies have found GC therapy can also produce neuromotor/cognitive deficits and selectively stunt the cerebellum. However, despite its continued use, relatively little is known about how exposure to this hormone might produce neurodevelopmental deficits. In this review, we use rodent and human research to provide evidence that GC therapy may disrupt cerebellar development through the rapid induction of apoptosis in the cerebellar external granule layer (EGL). The EGL is a transient proliferative region responsible for the production of over 90% of the neurons in the cerebellum. During normal development, endogenous GC stimulation is thought to selectively signal the elimination of the EGL once production of new neurons is complete. As a result, GC therapy may precociously eliminate the EGL before it can produce enough neurons for normal cerebellar function. It is hoped that this review may provide information for future clinical research in addition to translational guidance for the safer use of GC therapy. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Interorganellar Membrane Microdomains: Dynamic Platforms in the Control of Calcium Signaling and Apoptosis
Cells 2013, 2(3), 574-590; doi:10.3390/cells2030574
Received: 21 June 2013 / Revised: 23 July 2013 / Accepted: 26 July 2013 / Published: 2 August 2013
Cited by 7 | PDF Full-text (1259 KB) | HTML Full-text | XML Full-text
Abstract
The dynamic interplay among intracellular organelles occurs at specific membrane tethering sites, where two organellar membranes come in close apposition but do not fuse. Such membrane microdomains allow for rapid and efficient interorganelle communication that contributes to the maintenance of cell physiology. [...] Read more.
The dynamic interplay among intracellular organelles occurs at specific membrane tethering sites, where two organellar membranes come in close apposition but do not fuse. Such membrane microdomains allow for rapid and efficient interorganelle communication that contributes to the maintenance of cell physiology. Pathological conditions that interfere with the proper composition, number, and physical vicinity of the apposing membranes initiate a cascade of events resulting in cell death. Membrane contact sites have now been identified that tether the extensive network of the endoplasmic reticulum (ER) membranes with the mitochondria, the plasma membrane (PM), the Golgi and the endosomes/lysosomes. Thus far, the most extensively studied are the MAMs, or mitochondria associated ER membranes, and the ER-PM junctions that share functional properties and crosstalk to one another. Specific molecular components that define these microdomains have been shown to promote the interaction in trans between these intracellular compartments and the transfer or exchange of Ca2+ ions, lipids, and metabolic signaling molecules that determine the fate of the cell. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview DNA Methylation and Apoptosis Resistance in Cancer Cells
Cells 2013, 2(3), 545-573; doi:10.3390/cells2030545
Received: 25 May 2013 / Revised: 27 June 2013 / Accepted: 28 June 2013 / Published: 18 July 2013
Cited by 6 | PDF Full-text (461 KB) | HTML Full-text | XML Full-text
Abstract
Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between [...] Read more.
Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cancer and some new therapeutical strategies focus on inducing cell death in cancer cells. Nevertheless, cancer cells are resistant to treatment inducing cell death because of different mechanisms, such as DNA mutations in gene coding for pro-apoptotic proteins, increased expression of anti-apoptotic proteins and/or pro-survival signals, or pro-apoptic gene silencing mediated by DNA hypermethylation. In this context, aberrant DNA methylation patterns, hypermethylation and hypomethylation of gene coding for proteins implicated in apoptotic pathways are possible causes of cancer cell resistance. This review highlights the role of DNA methylation of apoptosis-related genes in cancer cell resistance. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview The Role of Tricho-Rhino-Phalangeal Syndrome (TRPS) 1 in Apoptosis during Embryonic Development and Tumor Progression
Cells 2013, 2(3), 496-505; doi:10.3390/cells2030496
Received: 4 February 2013 / Revised: 27 May 2013 / Accepted: 30 May 2013 / Published: 27 June 2013
Cited by 4 | PDF Full-text (179 KB) | HTML Full-text | XML Full-text
Abstract
TRPS1 is a GATA-type transcription factor that is closely related to human tricho-rhino-phalangeal syndrome (TRPS) types I and III, variants of an autosomal dominant skeletal disorder. During embryonic development, Trps1 represses Sox9 expression and regulates Wnt signaling pathways that determine the number [...] Read more.
TRPS1 is a GATA-type transcription factor that is closely related to human tricho-rhino-phalangeal syndrome (TRPS) types I and III, variants of an autosomal dominant skeletal disorder. During embryonic development, Trps1 represses Sox9 expression and regulates Wnt signaling pathways that determine the number of hair follicles and their normal morphogenesis. In the growth plate, Trps1 regulates chondrocytes condensation, proliferation, and maturation and phalangeal joint formation by functioning downstream of Gdf5 signaling and by targeting at Pthrp, Stat3 and Runx2. Also, Trps1 protein directly interacts with an activated form of Gli3. In embryonic kidneys, Trps1 functions downstream of BMP7 promoting the mesenchymal-to-epithelial transition, and facilitating tubule morphogenesis and ureteric bud branching. Moreover, Trps1 has been found to be closely related to tumorigenesis, invasion, and metastasis in prostate and breast cancers. It is interesting to note that during the development of hair follicles, bones, and kidneys, mutations in Trps1 cause, either directly or through crosstalk with other regulators, a notable change in cell proliferation and cell death. In this review, we will summarize the most recent studies on Trps1 and seek to elucidate the role for Trps1 in apoptotic regulation. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Apoptotic Cell Death in Neuroblastoma
Cells 2013, 2(2), 432-459; doi:10.3390/cells2020432
Received: 10 May 2013 / Revised: 30 May 2013 / Accepted: 8 June 2013 / Published: 20 June 2013
Cited by 3 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Neuroblastoma (NB) is one of the most common malignant solid tumors in childhood, which derives from the sympathoadrenal lineage of the neural crest and exhibits extremely heterogeneous biological and clinical behaviors. The infant patients frequently undergo spontaneous regression even with metastatic disease, [...] Read more.
Neuroblastoma (NB) is one of the most common malignant solid tumors in childhood, which derives from the sympathoadrenal lineage of the neural crest and exhibits extremely heterogeneous biological and clinical behaviors. The infant patients frequently undergo spontaneous regression even with metastatic disease, whereas the patients of more than one year of age who suffer from disseminated disease have a poor outcome despite intensive multimodal treatment. Spontaneous regression in favorable NBs has been proposed to be triggered by nerve growth factor (NGF) deficiency in the tumor with NGF dependency for survival, while aggressive NBs have defective apoptotic machinery which enables the tumor cells to evade apoptosis and confers the resistance to treatment. This paper reviews the molecules and pathways that have been recently identified to be involved in apoptotic cell death in NB and discusses their potential prospects for developing more effective therapeutic strategies against aggressive NB. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation
Cells 2013, 2(2), 330-348; doi:10.3390/cells2020330
Received: 15 April 2013 / Revised: 25 April 2013 / Accepted: 14 May 2013 / Published: 22 May 2013
Cited by 11 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
Resolution of acute inflammation is an active process that requires inhibition of further leukocyte recruitment and removal of leukocytes from inflamed sites. Emigrated neutrophils undergo apoptosis before being removed by scavenger macrophages. Recent studies using a variety of gene knockout, transgenic and [...] Read more.
Resolution of acute inflammation is an active process that requires inhibition of further leukocyte recruitment and removal of leukocytes from inflamed sites. Emigrated neutrophils undergo apoptosis before being removed by scavenger macrophages. Recent studies using a variety of gene knockout, transgenic and pharmacological strategies in diverse models of inflammation established neutrophil apoptosis as a critical control point in resolving inflammation. Analysis of death mechanisms revealed distinct features in executing the death program in neutrophils, which can be exploited as targets for controlling the lifespan of neutrophils. Indeed, anti-inflammatory and pro-resolution lipid mediators derived from essential fatty acids, such as lipoxin A4 and resolvin E1, autacoids and proteins, such as annexin A1 and TRAIL, and cyclin-dependent kinase inhibitors, can enhance the resolution of inflammation through induction of neutrophil apoptosis and promoting their removal by efferocytosis. In this review, we discuss recent advances in understanding the molecular basis of these actions, highlighting the potential of therapeutic induction of neutrophil apoptosis for dampening neutrophil-mediated tissue injury and inflammation underlying a variety of diseases. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Morphological Features of Organelles during Apoptosis: An Overview
Cells 2013, 2(2), 294-305; doi:10.3390/cells2020294
Received: 31 January 2013 / Revised: 24 March 2013 / Accepted: 19 April 2013 / Published: 8 May 2013
Cited by 6 | PDF Full-text (637 KB) | HTML Full-text | XML Full-text
Abstract
An apoptotic program leading to controlled cell dismantling implies perturbations of nuclear dynamics, as well as changes affecting the organelle structure and distribution. In human cancer cells driven to apoptosis by different stimuli, we have recently investigated the morphological properties of several [...] Read more.
An apoptotic program leading to controlled cell dismantling implies perturbations of nuclear dynamics, as well as changes affecting the organelle structure and distribution. In human cancer cells driven to apoptosis by different stimuli, we have recently investigated the morphological properties of several organelles, including mitochondria, lysosomes, endoplasmic reticulum and Golgi apparatus. In this review, we will discuss the body of evidence in the literature suggesting that organelles are generally relocated and/or degraded during apoptosis, irrespectively of the apoptogenic stimulus and cell type. Full article
(This article belongs to the Special Issue Apoptosis)
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Open AccessReview Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 Diabetes
Cells 2013, 2(2), 266-283; doi:10.3390/cells2020266
Received: 14 February 2013 / Revised: 3 April 2013 / Accepted: 5 April 2013 / Published: 26 April 2013
Cited by 4 | PDF Full-text (322 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic beta-cell apoptosis is an important feature of islets in type 2 diabetes. Apoptosis can occur through two major pathways, the extrinsic or death receptor mediated pathway, and the intrinsic or Bcl-2-regulated pathway. Hyperglycaemia, hyperlipidaemia and islet amyloid poly-peptide (IAPP) represent important [...] Read more.
Pancreatic beta-cell apoptosis is an important feature of islets in type 2 diabetes. Apoptosis can occur through two major pathways, the extrinsic or death receptor mediated pathway, and the intrinsic or Bcl-2-regulated pathway. Hyperglycaemia, hyperlipidaemia and islet amyloid poly-peptide (IAPP) represent important possible causes of increased beta-cell apoptosis. Hyperglycaemia induces islet-cell apoptosis by the intrinsic pathway involving molecules of the Bcl-2 family. High concentrations of palmitate also activate intrinsic apoptosis in islets cells. IAPP oligomers can induce apoptosis by both intrinsic and extrinsic pathways. IL-1b produced through NLRP3 inflammasome activation can also induce islet cell death. Activation of the NLRP3 inflammasome may not be important for glucose or palmitate induced apoptosis in islets but may be important for IAPP mediated cell death. Endoplasmic reticulum (ER) and oxidative stress have been observed in beta cells in type 2 diabetes, and these could be the link between upstream metabolic abnormalities and downstream apoptotic machinery. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword
Cells 2013, 2(2), 202-223; doi:10.3390/cells2020202
Received: 4 February 2013 / Revised: 5 March 2013 / Accepted: 12 March 2013 / Published: 26 March 2013
Cited by 9 | PDF Full-text (523 KB) | HTML Full-text | XML Full-text
Abstract
First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis [...] Read more.
First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Regulation of Apoptosis by Inhibitors of Apoptosis (IAPs)
Cells 2013, 2(1), 163-187; doi:10.3390/cells2010163
Received: 5 February 2013 / Revised: 4 March 2013 / Accepted: 5 March 2013 / Published: 14 March 2013
Cited by 22 | PDF Full-text (190 KB) | HTML Full-text | XML Full-text
Abstract
Inhibitors of Apoptosis (IAPs) are a family of proteins with various biological functions including regulation of innate immunity and inflammation, cell proliferation, cell migration and apoptosis. They are characterized by the presence of at least one N-terminal baculoviral IAP repeat (BIR) [...] Read more.
Inhibitors of Apoptosis (IAPs) are a family of proteins with various biological functions including regulation of innate immunity and inflammation, cell proliferation, cell migration and apoptosis. They are characterized by the presence of at least one N-terminal baculoviral IAP repeat (BIR) domain involved in protein-protein interaction. Most of them also contain a C-terminal RING domain conferring an E3-ubiquitin ligase activity. In drosophila, IAPs are essential to ensure cell survival, preventing the uncontrolled activation of the apoptotic protease caspases. In mammals, IAPs can also regulate apoptosis through controlling caspase activity and caspase-activating platform formation. Mammalian IAPs, mainly X-linked IAP (XIAP) and cellular IAPs (cIAPs) appeared to be important determinants of the response of cells to endogenous or exogenous cellular injuries, able to convert the survival signal into a cell death-inducing signal. This review highlights the role of IAP in regulating apoptosis in Drosophila and Mammals. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)
Cells 2013, 2(1), 136-162; doi:10.3390/cells2010136
Received: 24 December 2012 / Revised: 5 February 2013 / Accepted: 21 February 2013 / Published: 6 March 2013
Cited by 22 | PDF Full-text (808 KB) | HTML Full-text | XML Full-text
Abstract
Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with [...] Read more.
Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca2+. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca2+ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca2+-dependent protein(s) or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP) complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome. Full article
(This article belongs to the Special Issue Apoptosis)
Open AccessReview The Anti-Apoptotic Role of Neurotensin
Cells 2013, 2(1), 124-135; doi:10.3390/cells2010124
Received: 24 January 2013 / Revised: 15 February 2013 / Accepted: 26 February 2013 / Published: 4 March 2013
Cited by 3 | PDF Full-text (192 KB) | HTML Full-text | XML Full-text
Abstract
The neuropeptide, neurotensin, exerts numerous biological functions, including an efficient anti-apoptotic role, both in the central nervous system and in the periphery. This review summarizes studies that clearly evidenced the protective effect of neurotensin through its three known receptors. The pivotal involvement [...] Read more.
The neuropeptide, neurotensin, exerts numerous biological functions, including an efficient anti-apoptotic role, both in the central nervous system and in the periphery. This review summarizes studies that clearly evidenced the protective effect of neurotensin through its three known receptors. The pivotal involvement of the neurotensin receptor-3, also called sortilin, in the molecular mechanisms of the anti-apoptotic action of neurotensin has been analyzed in neuronal cell death, in cancer cell growth and in pancreatic beta cell protection. The relationships between the anti-apoptotic role of neurotensin and important physiological and pathological contexts are discussed in this review. Full article
(This article belongs to the Special Issue Apoptosis)

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