Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Regulated Cell Death”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2000

In vivo regulation of cell death by embryonic (pro)insulin and the insulin receptor during early retinal neurogenesis.

Programmed cell death is an established developmental process in the nervous system. Whereas the regulation and the developmental role of neuronal cell death have been widely demonstrated, the relevance of cell death during early neurogenesis, the cells affected and the identity of regulatory local growth factors remain poorly characterized. We have previously described specific in vivo patterns of apoptosis during early retinal neurogenesis, and that exogenous insulin acts as survival factor (Díaz, B., Pimentel, B., De Pablo, F. and de la Rosa, E. J. (1999) Eur. J. Neurosci. 11, 1624-1632). Proinsulin mRNA was found to be expressed broadly in the early embryonic chick retina, and decreased later between days 6 and 8 of embryonic development, when there was increased expression of insulin-like growth factor I mRNA, absent or very scarce at earlier stages. Consequently, we studied whether proinsulin and/or insulin ((pro)insulin) action in prevention of cell death has physiological relevance during early neural development. In ovo treatment at day 2 of embryonic development with specific antibodies against (pro)insulin or the insulin receptor induced apoptosis in the neuroretina. The distribution of apoptotic cells two days after the blockade was similar to naturally occurring cell death, as visualized by TdT-mediated dUTP nick end labeling. The apoptosis induced by the insulin receptor blockade preferentially affected to the Islet1/2 positive cells, that is, the differentiated retinal ganglion cells. In parallel, the insulin survival effect on cultured retinas correlated with the activation of Akt to a greater extent than with the activation of MAP kinase. These results suggest that the physiological cell death occurring in early stages of retinal development is regulated by locally produced (pro)insulin through the activation of the Akt survival pathway.

Animals↗
PubMed2000

Uncoupling salicylic acid-dependent cell death and defense-related responses from disease resistance in the Arabidopsis mutant acd5.

Salicylic acid (SA) is required for resistance to many diseases in higher plants. SA-dependent cell death and defense-related responses have been correlated with disease resistance. The accelerated cell death 5 mutant of Arabidopsis provides additional genetic evidence that SA regulates cell death and defense-related responses. However, in acd5, these events are uncoupled from disease resistance. acd5 plants are more susceptible to Pseudomonas syringae early in development and show spontaneous SA accumulation, cell death, and defense-related markers later in development. In acd5 plants, cell death and defense-related responses are SA dependent but they do not confer disease resistance. Double mutants with acd5 and nonexpressor of PR1, in which SA signaling is partially blocked, show greatly attenuated cell death, indicating a role for NPR1 in controlling cell death. The hormone ethylene potentiates the effects of SA and is important for disease symptom development in Arabidopsis. Double mutants of acd5 and ethylene insensitive 2, in which ethylene signaling is blocked, show decreased cell death, supporting a role for ethylene in cell death control. We propose that acd5 plants mimic P. syringae-infected wild-type plants and that both SA and ethylene are normally involved in regulating cell death during some susceptible pathogen infections.

Apoptosis↗
PubMed1999

Hormonally regulated programmed cell death in barley aleurone cells

Cell death was studied in barley (cv Himalaya) aleurone cells treated with abscisic acid and gibberellin. Aleurone protoplasts incubated in abscisic acid remained viable in culture for at least 3 weeks, but exposure to gibberellin initiated a series of events that resulted in death. Between 4 and 8 days after incubation in gibberellin, >70% of all protoplasts died. Death, which occurred after cells became highly vacuolated, was manifest by an abrupt loss of plasma membrane integrity followed by rapid shrinkage of the cell corpse. Hydrolysis of DNA began before death and occurred as protoplasts ceased production of alpha-amylase. DNA degradation did not result in the accumulation of discrete low molecular weight fragments. DNA degradation and cell death were prevented by LY83583, an inhibitor of gibberellin signaling in barley aleurone. We conclude that cell death in aleurone cells is hormonally regulated and is the final step of a developmental program that promotes successful seedling establishment.

Journal Article↗
PubMed1999

[Apoptosis and cancer].

Apoptosis or programmed cell death is a form of regulated cell death that represents an important biological principle in tissue development and homeostasis. Its regulation appears to be perturbed in several major diseases, including cancer. The control of cell death events is extremely complex at the genetic and biochemical levels. It has been suggested that genes or factors that suppress apoptosis are essential components of carcinogenesis. The complete mechanisms implicated in apoptosis remains an issue for a future investigation. Details of how the death pathway itself is initiated, will provide a firm basis for the development of agents capable of eliciting the process in chemoresistant tumours.

Apoptosis↗
PubMed2000

Mechanisms of apoptosis.

Programmed cell death plays critical roles in a wide variety of physiological processes during fetal development and in adult tissues. In most cases, physiological cell death occurs by apoptosis as opposed to necrosis. Defects in apoptotic cell death regulation contribute to many diseases, including disorders where cell accumulation occurs (cancer, restenosis) or where cell loss ensues (stroke, heart failure, neurodegeneration, AIDS). In recent years, the molecular machinery responsible for apoptosis has been elucidated, revealing a family of intracellular proteases, the caspases, which are responsible directly or indirectly for the morphological and biochemical changes that characterize the phenomenon of apoptosis. Diverse regulators of the caspases have also been discovered, including activators and inhibitors of these cell death proteases. Inputs from signal transduction pathways into the core of the cell death machinery have also been identified, demonstrating ways of linking environmental stimuli to cell death responses or cell survival maintenance. Knowledge of the molecular mechanisms of apoptosis is providing insights into the causes of multiple pathologies where aberrant cell death regulation occurs and is beginning to provide new approaches to the treatment of human diseases.

Animals↗
PubMed2001

Mouse models of cell death.

Cell death is critical for the development and orderly maintenance of cellular homeostasis in metazoans. Developmental genetics in model systems, including Caenorhabditis elegans and Drosophila melanogaster, have helped to identify and order the components of cell-death pathways. An even more complex network of apoptotic pathways has evolved in higher organisms that possess homologs within each set of cell-death regulators. Whereas biochemical studies provide details of molecular mechanisms, genetic models reveal the essential physiologic roles. Transgenic and gene-ablated mice have helped to elucidate mammalian apoptotic pathways and identify the principal effect of each cell death regulator. Here, we review the details of the apoptotic machinery as revealed by mice deficient in critical components of cell-death pathways; we concentrate on cell-death regulators classified as members of the caspase and Bcl2 families or, broadly, as adaptors and mitochondrial released factors.

Animals↗
PubMed2006

Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death.

Galectin-1 kills immature thymocytes and activated peripheral T cells by binding to glycans on T cell glycoproteins including CD7, CD45, and CD43. Although roles for CD7 and CD45 in regulating galectin-1-induced death have been described, the requirement for CD43 remains unknown. We describe a novel role for CD43 in galectin-1-induced death, and the effects of O-glycan modification on galectin-1 binding to CD43. Loss of CD43 expression reduced galectin-1 death of murine thymocytes and human T lymphoblastoid cells, indicating that CD43 is required for maximal T cell susceptibility to galectin-1. CD43, which is heavily O-glycosylated, contributes a significant fraction of galectin-1 binding sites on T cells, as T cells lacking CD43 bound approximately 50% less galectin-1 than T cells expressing CD43. Although core 2 modification of O-glycans on other glycoprotein receptors is critical for galectin-1-induced cross-linking and T cell death, galectin-1 bound to CD43 fusion proteins modified with either unbranched core 1 or branched core 2 O-glycans and expression of core 2 O-glycans did not enhance galectin-1 binding to CD43 on T cells. Moreover, galectin-1 binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T cell surface. Thus, CD43 bearing either core 1 or core 2 O-glycans can positively regulate T cell susceptibility to galectin-1, identifying a novel function for CD43 in controlling cell death. In addition, these studies demonstrate that different T cell glycoproteins on the same cell have distinct requirements for glycan modifications that allow recognition and cross-linking by galectin-1.

Animals↗
PubMed2006

Lithium increases bcl-2 expression in chick cochlear nucleus and protects against deafferentation-induced cell death.

Approximately 20-30% of neurons in the avian cochlear nucleus (nucleus magnocellularis) die following deafferentation (i.e. deafness produced by cochlea removal) and the remaining neurons show a decrease in soma size. Cell death is generally accepted to be a highly regulated process involving various pro-survival and pro-death molecules. One treatment that has been shown to modify the expression of these molecules is chronic administration of lithium. The present experiments examined whether lithium treatment can protect neurons from deafferentation-induced cell death. Post-hatch chicks were treated with LiCl or saline for 17 consecutive days, beginning on the day of hatching. On the 17th day, a unilateral cochlea ablation was performed. Five days following surgery, the nucleus magnocellularis neurons were counted stereologically on opposite sides of the same brains. Lithium reduced deafferentation-induced cell death by more than 50% (9.8% cell death as compared with 22.4% in saline-treated subjects). Lithium did not affect cell number on the intact side of the brain. Lithium also did not prevent the deafferentation-induced decrease in soma size, suggesting a dissociation between the mechanisms involved in the afferent control of soma size and those involved in the afferent control of cell viability. A possible mechanism for lithium's neuroprotective influence was examined in a second set of subjects. Previous studies suggest that the pro-survival molecule, bcl-2, may play a role in regulating cell death following deafferentation. Tissues from lithium- and saline-treated subjects were examined using immunocytochemistry. Chronic administration of lithium dramatically increased the expression of bcl-2 protein in nucleus magnocellularis neurons. These data suggest that lithium may impart its neuroprotective effect by altering the expression of molecules that regulate cell death.

Afferent Pathways↗
PubMed2001

NMDA receptor regulation of cell death in the rat olfactory bulb.

Cell death is widespread in the developing nervous system and is under complex regulation by numerous intra- and intercellular mechanisms. Blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been shown to promote cell death in the developing brain (Ikonomidou et al., 1999), suggesting that afferent functional activation is an important regulator of cell survival. The olfactory bulb, the first central relay for olfactory information from the nose, is well suited for examining the role of afferent activity in neuronal development. Functional deprivation is easily performed by surgical blockade of airflow to one side of the nasal passage, which results in dramatic alterations in postnatal development of the bulb (Brunjes, 1994), including enhanced neuronal loss (Frazier and Brunjes, 1988; Najbauer and Leon, 1995). The present report examined the specific role of NMDA receptor activation in regulating cell survival within the rat bulb. Pharmacological blockade of receptors with the noncompetitive channel blocker MK-801 (3 x 0.5 mg/kg i.p.) resulted in profound increases in cell death within 24 h. Furthermore, in contrast to other regions, where the effects of receptor blockade were confined to the first 2 postnatal weeks (Ikonomidou et al., 1999), enhancement of cell death was seen in the deeper granule cell-containing regions of the bulb with injections as late as postnatal day 28. In addition, the effects of MK-801 were much more dramatic than those seen after unilateral naris closure, suggesting that NMDA receptor activation may mediate additional survival pathways in the bulb beyond that provided by first nerve input.

Animals↗
PubMed2004

Inactivation of Drosophila Apaf-1 related killer suppresses formation of polyglutamine aggregates and blocks polyglutamine pathogenesis.

Huntington's disease (HD) is caused by expansion of a polyglutamine tract near the N-terminal of huntingtin. Mutant huntingtin forms aggregates in striatum and cortex, where extensive cell death occurs. We used a Drosophila polyglutamine peptide model to assess the role of specific cell death regulators in polyglutamine-induced cell death. Here, we report that polyglutamine-induced cell death was dramatically suppressed in flies lacking Dark, the fly homolog of human Apaf-1, a key regulator of apoptosis. Dark appeared to play a role in the accumulation of polyglutamine-containing aggregates. Suppression of cell death, caspase activation and aggregate formation were also observed when mutant huntingtin exon 1 was expressed in homozygous dark mutant animals. Expanded polyglutamine induced a marked increase in expression of Dark, and Dark was observed to colocalize with ubiquitinated protein aggregates. Apaf-1 also was found to colocalize with huntingtin-containing aggregates in a murine model and HD brain, suggesting a common role for Dark/Apaf-1 in polyglutamine pathogenesis in invertebrates, mice and man. These findings suggest that limiting Apaf-1 activity may alleviate both pathological protein aggregation and neuronal cell death in HD.

Animals↗
PubMed2004

Deadly decisions: the role of genes regulating programmed cell death in human preimplantation embryo development.

Human preimplantation embryo development is prone to high rates of early embryo wastage, particularly under current in vitro culture conditions. There are many possible underlying causes for embryo demise, including DNA damage, poor embryo metabolism and the effect of suboptimal culture media, all of which could result in an imbalance in gene expression and the failed execution of basic embryonic decisions. In view of the complex interactions involved in embryo development, a thorough understanding of these parameters is essential to improving embryo quality. An increasing body of evidence indicates that cell fate (i.e. survival/differentiation or death) is determined by the outcome of specific intracellular interactions between pro- and anti-apoptotic proteins, many of which are expressed during oocyte and preimplantation embryo development. The recent availability of mutant mice lacking expression of various genes involved in the regulation of cell survival has enabled rapid progress towards identifying those molecules that are functionally important for normal oocyte and preimplantation embryo development. In this review we will discuss the current understanding of the regulation of cell death gene expression during preimplantation embryo development, with a focus on human embryology and a discussion of animal models where appropriate.

Animals↗
PubMed1997

Cell death in the regulation of immune responses.

Cell death is an integral part of the functioning of the immune system. For T cells, potentially autoreactive or 'useless' cells are removed through apoptosis in response to signals (or lack of signals) from their T cell receptor complex. A myriad of proteins that can initiate or protect cells from cell death have recently been identified.

Animals↗
PubMed2000

Regulation of cell death in flower petals.

The often rapid and synchronous programmed death of petal cells provides a model system to study molecular aspects of organ senescence. The death of petal cells is preceded by a loss of membrane permeability, due in part to increases in reactive oxygen species that are in turn related to up-regulation of oxidative enzymes and to a decrease in activity of certain protective enzymes. The senescence process also consists of a loss of proteins caused by activation of various proteinases, a loss of nucleic acids as nucleases are activated, and enzyme-mediated alterations of carbohydrate polymers. Many of the genes for these senescence-associated enzymes have been cloned. In some flowers, the degradative changes of petal cells are initiated by ethylene; in others, abscisic acid may play a role. External factors such as pollination, drought and temperature stress also affect senescence, perhaps by interacting with hormones normally produced by the flowers. Signal transduction may involve G-proteins, calcium activity changes and the regulation of protein phosphorylation and dephosphorylation. The efficacy of the floral system as well as the research tools now available make it likely that important information will soon be added to our knowledge of the molecular mechanisms involved in petal cell death.

Apoptosis↗
PubMed2004

Comparative effects of various nitric oxide donors on ferritin regulation, programmed cell death, and cell redox state in plant cells.

Past studies investigating the regulatory functions of nitric oxide (NO) in plant cells have utilized various NO-donors that release NO in different redox forms, which has lead to problems in the interpretation of data. In the present study, the effects of different NO-donors releasing NO with either NO+ (SNP) or NO' (SNAP, GSNO, NOC-18) character have been compared in plant cells. In particular, ferritin regulation, programmed cell death, cellular redox state, and ROS-scavenging enzymes in Arabidopsis thaliana and Nicotiana tabacum cells were examined. The results show that SNP behaves differently than the other NO-donors tested; indeed, SNP induces accumulation of ferritin transcripts in Arabidopsis, whereas SNAP inhibits its accumulation. Moreover, among the assortment of donors tested, only SNP caused programmed cell death and suppression of ROS-scavenging systems.

Apoptosis↗
PubMed2005

Lozenge directly activates argos and klumpfuss to regulate programmed cell death.

We show that reducing the activity of the Drosophila Runx protein Lozenge (Lz) during pupal development causes a decrease in cell death in the eye. We identified Lz-binding sites in introns of argos (aos) and klumpfuss (klu) and demonstrate that these genes are directly activated targets of Lz. Loss of either aos or klu reduces cell death, suggesting that Lz promotes apoptosis at least in part by regulating aos and klu. These results provide novel insights into the control of programmed cell death (PCD) by Lz during Drosophila eye development.

Animals↗
PubMed2006

Caspase-containing complexes in the regulation of cell death and inflammation.

Caspases are a family of cysteine proteases that are essential in the initiation and execution of apoptosis and the proteolytic maturation of inflammatory cytokines such as IL-1beta and IL-18. Caspases can be subdivided into those that have a large prodomain and those that have not. In general, apoptotic and inflammatory signalling pathways are initiated when large-prodomain caspases are recruited to large protein complexes via homotypic interactions involving death domain folds. The formation of these specialised multimeric platforms involves three major functions: (1) the sensing of cellular stress, damage, infection or inflammation; (2) multimerisation of the platform; and (3) recruitment and conformational activation of caspases. In this overview we discuss the complexes implicated in the regulation of cell death and inflammatory processes such as the death-inducing signalling complex (DISC), the apoptosome, the inflammasomes and the PIDDosome. We describe their sensing functions, compositions and functional outcomes. Inhibitory protein families such as FLIPs and CARD-only proteins prevent the recruitment of caspases in these sensing complexes, avoiding inappropriate initiation of cell death or inflammation.

Animals↗
PubMed1999

Glutathione and the regulation of cell death.

The association of elevated levels of glutathione and glutathione S-transferases with the development of resistance to alkylating agents was established more than 10 years ago. Although numerous similar reports have appeared since this time work in this area has tended to dwindle as interest has become focused on more fashionable areas of drug resistance research. However, over the past 3 or 4 years there has been a revival of interest in the study of glutathione and glutathione utilising enzymes driven by recent discoveries which have implicated redox balance as an important regulator of cell death and transmembrane drug transport. In this brief review I highlight some of the more rapid areas of advance.

ATP-Binding Cassette Transporters↗
PubMed1997

Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice.

The intracellular balance between pro- and antiapoptotic members of the Bcl-2 gene family is thought to regulate cell death. Targeted disruption of bcl-x, a death repressing member, causes massive cell death of immature neurons in the developing mouse CNS, whereas targeted disruption of bax, a proapoptotic member, blocks the death of specific populations of sympathetic and motor neurons. In the present study, mice deficient in both Bcl-xL and Bax (bcl-x-/-/bax-/-) are used to examine the relative significance and potential interactions of Bcl-xL and Bax during early CNS development. bcl-x-/-/bax-/- mice demonstrate greatly reduced levels of apoptosis both in vivo and in vitro compared with the CNS of Bcl-xL-deficient mice, as assessed by histology and terminal deoxytransferase-mediated deoxyuridine triphosphate nick end-labeling. Bax-deficient mice, however, contain occasional apoptotic cells in the developing CNS, and cultures of bax-deficient telencephalic cells demonstrate similar levels of apoptosis as wild-type cultures. These results suggest that Bax critically interacts with Bcl-xL to regulate survival of immature neurons, but indicate that other cell death regulating proteins, in addition to Bcl-xL and Bax, also function during CNS development.

Animals↗