Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed 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 505 records · Page 28Linked to original sources
PubMed1992

A truncated erythropoietin receptor that fails to prevent programmed cell death of erythroid cells.

A form of the human erythropoietin receptor (EPOR) was identified in which the cytoplasmic region is truncated by alternative splicing. The truncated form of the receptor (EPOR-T) is the most prevalent form of EPOR in early-stage erythroid progenitor cells, but the full-length EPOR (EPOR-F) becomes the most prevalent form in late-stage progenitors. EPOR-T can transduce a mitogenic signal. However, cells transfected with EPOR-T are more prone to programmed cell death than those expressing EPOR-F. EPOR-F may transduce a signal to prevent programmed cell death that is independent of the mitogenic signal, and alternative splicing of the EPOR gene may have an important role in erythropoiesis.

Amino Acid Sequence↗
PubMed2006

Using Ciona to study developmental programmed cell death.

Ciona intestinalis, a member of Tunicates, the closest group to vertebrates, has emerged as an appropriate organism for the study of developmentally regulated programmed cell death. First, because massive phases of apoptosis occur all along embryogenesis. Second, because the lecithotrophic mode of development is associated with autophagic process occurring during juvenile formation. Third, because the biochemical cell death machinery is close to that found in mammals. Altogether, the Ciona system contributes to identify new specific regulatory pathways and to explain how molecular mechanisms of programmed cell death evolved from invertebrates to vertebrates.

Animals↗
PubMed1997

[Induction of cell differentiation and programmed cell death in amphibian metamorphosis].

Both the phenomena, the cell growth and differentiation, and the programmed cell death, are involved in the reconstruction of body from larval type to adult type during amphibian metamorphosis. Since all of metamorphic events are triggered by increase of plasma thyroid hormone level, the reconstruction of body during metamorphosis will provide useful biological system for analyzing the mechanism of hormonal induction of cell differentiation and programmed cell death. Induction of death of skein-type epidermal basal cells in tail skin of bullfrog tadpoles was involved in cell cycle arrest caused by triiodothyronine (T3). On the other hand, induction of adult type stratified and cornified epidermis was involved in T3-induction of the growth and differentiation of non-skein type epidermal basal cells in body skin. Developmental origin of these two different basal cells should be clarified. Analysis of adult type epidermal keratin expression during Xenopus metamorphosis revealed that enhanced transcription of adult type gene by synergism between T3 and glucocorticoid. Since receptors of these two hormones are belong to the same members of steroid receptor super family, interaction of hormones and hormone receptors should be studied for clarifying the molecular mechanism of the hormonal synergism at a transcription level. Programmed muscle cell death is important in tail degeneration as well as in the larval-to-adult conversion of the dorsal body muscle cell of Xenopus laevis during metamorphosis. In the tail, only death of larval type muscle cells occur. However, in the body, both the death of larval type muscle cells and new myogenesis (the growth and differentiation of adult type cells) occur to form adult skeletal muscles. The new myogenesis area expanded in a wave-like fashion with an anteroposterior gradient during metamorphic climax stage. The area of muscle cell death expanded like a wave from the base of the tail to the anterior and posterior side. Growth, differentiation and death of muscle cells were induced by T3. The origin of adult satellite cells for new myogenesis should be clarified in order to understand the mechanism of skeletal muscle development during metamorphosis.

Amphibians↗
PubMed1998

Programmed cell death in nodular palmar fibromatosis (Morbus Dupuytren).

The regular loss of cellularity during involutional phase of nodular palmar fibromatosis (Morbus Dupuytren) indicates a regulated process known as programmed cell death (apoptosis). Using the TUNEL method apoptosis-related DNA fragmentation is detected in numerous cells as a characteristic feature of fibromatosis noduli of involutional phase. By means of double labelling technique, alpha-smooth muscle actin immunohistochemistry and TUNEL method for apoptosis, it is demonstrated that the cells which underwent apoptotosis are myofibroblasts. As anticipated, the antidote to apoptosis bcl-2 is not detected in involutional phase, but neither it is evidenced in proliferative phase. Immunohistochemically, Fas/APO-1 is shown to be existent in a very small number of fibroblasts in involutional phase. However, in view of the high number of TUNEL-stained cells a significance in regulating apoptosis in nodular palmar fibromatosis seems improbable. Taking into account that the development of the fibromatosis noduli, the expression of myofibroblast phenotype, basement membrane formation and growth factor expression including TGF beta culminates in involutional phase the initiation of apoptotic cell death can be discussed in relation to these growth factors and matrix protein action and the programmed cell death may be considered as the final step of myofibroblast phenotype evolution.

Apoptosis↗
PubMed1994

Naturally occurring cell death in the developing cerebral cortex of the rat. Evidence of apoptosis-associated internucleosomal DNA fragmentation.

Naturally occurring dead cells in the developing rat neocortex, subcortical white matter and hippocampus, which increase in number during the first postnatal week and decrease thereafter to disappear by the end of the first month, were examined by in situ labeling of nuclear DNA fragmentation. These cells showed peripheral chromatin condensation or extremely dark, often fragmented, nuclei. Southern hybridization following agarose gel electrophoresis of DNA extracted from the developing cortex, but not from adult brain, showed a 'ladder' pattern which is typical of internucleosomal DNA fragmentation. Taken together these results show that naturally occurring cell death (programmed cell death) in the developing cerebral cortex has the morphology of apoptosis and is associated with endonuclease activation.

Aging↗
PubMed2004

On the evolution of erythrocyte programmed cell death: apoptosis of Rana esculenta nucleated red blood cells involves cysteine proteinase activation and mitochondrion permeabilization.

Batracian Rana esculenta erythrocytes cell death induced by either calcium influx, or staurosporine, involves typical apoptotic phenotype. Our data reveal: (i) a drastic modification of the cell morphology with loss of the ellipsoidal form as assessed by phase contrast microscopy and scanning electron microscopy; (ii) an exposure of the phosphatidylserine residues in the outer leaflet of the cell membrane; (iii) a caspase-3-like activity; (iv) a mitochondrial membrane potential (Delta Psi m) loss; and (v) a chromatin condensation and fragmentation. Erythrocyte chromatin condensation and fragmentation are prevented by caspase and calpain peptide inhibitors. These inhibitors also prevent Delta Psi m loss supporting the idea that mitochondria is a central sensor for Rana erythrocytes cell death. Our observations highlight the conservation of the programmed cell death machinery in erythrocytes across kingdom.

Animals↗
PubMed1991

Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia.

In the present study, we examined the possibility that granulosa cell death during ovarian follicular atresia occurs by apoptosis (programmed cell death). To investigate this possibility, atresia was induced in immature female rats by injecting 15 IU PMSG. Controls received either vehicle or no treatment. PMSG-treated animals were killed on days 1-5 post-injection while controls were killed on days 1 or 5. The onset of atresia was assessed histologically by light microscopic inspection of 5 microns tissue sections and functionally by quantification of serum progesterone and estrogen levels. Apoptosis is characterized by the cleavage of genomic DNA into oligonucleosomal length fragments by a Ca2+/Mg(2+)-dependent endogenous endonuclease. Such fragments form a distinctive ladder pattern when separated electrophoretically. Accordingly, the occurrence of apoptosis in granulosa cells was assessed by examining the pattern of fragmented DNA in cell lysates after agarose gel electrophoresis. Gels were stained with ethidium bromide and DNA visualized by UV transillumination. The earliest morphological signs of atresia were detected 4 days after PMSG injection as evidenced by degeneration and detachment of granulosa cells from the basal lamina. Serum estrogen increased from basal to levels 7-fold over controls by day 3 after PMSG treatment, falling to control values by day 4 and thereafter. In contrast, progesterone remained basal for the first 3 days, rising to levels 3-fold and 8-fold above controls 4 and 5 days after PMSG treatment, respectively. Such shifts in the ratio of estrogen to progesterone production are known to be characteristic of follicular atresia. Finally, electrophoretic analysis of low mol wt DNA in granulosa cell lysates revealed a definitive ladder pattern of oligonucleosomal length DNA fragments (characteristic of apoptosis) on days 4 and 5 after PMSG injection. This pattern was not detectable on days 1 and 2 after treatment. Lysates obtained 3 days after PMSG treatment showed a faint apoptotic-like pattern of DNA fragments; a result consistent with other systems in which DNA cleavage begins before any morphological signs of death. Interestingly, a ladder pattern of DNA fragments was present in control lysates suggesting that granulosa cell death under normal (vs. induced) conditions of atresia in immature rats occurs by apoptosis. These data demonstrate an intimate association between apoptotic-like events and dying granulosa cells and thus support the possibility that apoptosis is involved in the induction of follicular atresia.

Animals↗
PubMed2005

Extracellular heat shock protein 70: a critical component for motoneuron survival.

The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and in vitro. Considering this apparent dependence, we examined whether a specific component of the stress response mediates motoneuron survival in trophic factor-deprived environments. We demonstrate that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival. Conversely, depletion of HSP70 from chick muscle extract (MEx) potently reduces the survival-promoting activity of MEx. Additionally, exogenous treatment with or spinal cord overexpression of Hsp70 enhances motoneuron survival in vivo during the period of naturally occurring cell death [programmed cell death (PCD)]. Hindlimb muscle cells and lumbar spinal astrocytes readily secrete HSP70 in vitro, suggesting potential physiological sources of extracellular Hsp70 for motoneurons. However, in contrast to exogenous treatment with or overexpression of Hsp70 in vivo, muscle-targeted injections of this factor in an ex vivo preparation fail to attenuate motoneuron PCD. These data (1) suggest that motoneuron survival requirements may extend beyond classical trophic factors to include HSP70, (2) indicate that the source of this factor is instrumental in determining its trophic function, and (3) may therefore influence therapeutic strategies designed to increase motoneuron Hsp70 signaling during disease or injury.

Animals↗
PubMed2001

Tomato ribonuclease LX with the functional endoplasmic reticulum retention motif HDEF is expressed during programmed cell death processes, including xylem differentiation, germination, and senescence.

We have studied the subcellular localization of the acid S-like ribonuclease (RNase) LX in tomato (Lycopersicon esculentum Mill.) cells using a combination of biochemical and immunological methods. It was found that the enzyme, unexpectedly excluded from highly purified vacuoles, accumulates in the endoplasmic reticulum. The evidence that RNase LX is a resident of the endoplasmic reticulum (ER) is supported by an independent approach showing that the C-terminal peptide HDEF of RNase LX acts as an alternative ER retention signal in plants. For functional testing, the cellular distribution of chimeric protein constructs based on a marker protein, Brazil nut (Bertholletia excelsa) 2S albumin, was analyzed immunochemically in transgenic tobacco (Nicotiana tabacum) plants. Here, we report that the peptide motif is necessary and sufficient to accumulate 2S albumin constructs of both vacuolar and extracellular final destinations in the ER. We have shown immunochemically that RNase LX is specifically expressed during endosperm mobilization and leaf and flower senescence. Using immunofluorescence, RNase LX protein was detected in immature tracheary elements, suggesting a function in xylem differentiation. These results support a physiological function of RNase LX in selective cell death processes that are also thought to involve programmed cell death. It is assumed that RNase LX accumulates in an ER-derived compartment and is released by membrane disruption into the cytoplasma of those cells that are intended to undergo autolysis. These processes are accompanied by degradation of cellular components supporting a metabolic recycling function of the intracellular RNase LX.

Amino Acid Motifs↗
PubMed2003

Estradiol attenuates programmed cell death after stroke-like injury.

Estradiol is a known neurotrophic and neuroprotective factor. Our previous work demonstrated that replacement with physiological concentrations of estradiol protects the cortex against middle cerebral artery occlusion (MCAO)-induced cell death. The cerebral cortex exhibits caspase-dependent programmed cell death (PCD) in many models of focal cerebral ischemia. We hypothesized that estradiol attenuates PCD during stroke injury. The current study explored the temporospatial pattern of markers of PCD, their relationship to the evolution of injury, and their modulation by estradiol. Rats were ovariectomized and treated with either estradiol or vehicle. One week later, rats underwent MCAO, and brains were collected at 1, 4, 8, 16, and 24 hr. We assessed the temporospatial evolution of infarction volume, DNA fragmentation, and levels of spectrin cleavage products in ischemic cortex. Estradiol led to a delay and attenuation of injury-mediated DNA fragmentation as early as 8 hr after MCAO. Estradiol also dramatically reduced the level of the 120 kDa caspase-mediated spectrin breakdown product (SBDP120) at 4 hr but not at 8 or 16 hr. The SBDP150, produced by caspase and calpain, showed peak levels at 16 hr but was not altered by estradiol. These results strongly suggest that estradiol protects the ischemic cortex by attenuating PCD, thereby reducing caspase activity, DNA fragmentation, and subsequently, overall cell death. These studies deepen our understanding of the mechanisms underlying estrogen-mediated neuroprotection.

Animals↗
PubMed1995

Apoptosis, oncosis, and necrosis. An overview of cell death.

The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.

Animals↗
PubMed1992

Correlation of calcineurin phosphatase activity and programmed cell death in murine T cell hybridomas.

Ligation of T cell receptor/CD3 complexes induces programmed cell death, or apoptosis, in immature thymocytes and many T cell hybridomas. While it has been demonstrated that T cell receptor-mediated apoptosis requires an increase in intracellular calcium concentration, the specific calcium-dependent signalling events leading to cell death are poorly defined. We have previously shown that T cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently, it has been determined that these agents inhibit the activity of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay which measures calcineurin activity in cell lysates, we find that calcineurin-dependent dephosphorylation of a phosphopeptide substrate is potently inhibited in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate that the level of cellular calcineurin activity correlates closely with the ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a critical mediator of T cell receptor/CD3 signalling leading to programmed cell death in T cell hybridomas.

Amino Acid Sequence↗
PubMed1995

Cytokines and programmed cell death in burkitt lymphoma cells.

Tumour necrosis Factor (TNF), Interleukin 1alpha and beta (IL-alpha and IL-beta), Interleukin 7 (IL-7) and Stem Cell Factor (SCF) are cytokines synthesized by immune system cells under stimulation of various agents. Apoptosis, or programmed cell death, is a process that appears in response to specific stimuli, apparently following an intrinsic program. In this work we examined, in RA-1 human lymphoblastoid B cell line, the effect induced by different cytokines in cell proliferation and in programmed cell death. After 48 hours of treatment is present an antiproliferative affects, detected by 3H-thymidine incorporation and morphological changes related to apoptotic process.

Apoptosis↗
PubMed1998

The regulation of reactive oxygen species production during programmed cell death.

Reactive oxygen species (ROS) are thought to be involved in many forms of programmed cell death. The role of ROS in cell death caused by oxidative glutamate toxicity was studied in an immortalized mouse hippocampal cell line (HT22). The causal relationship between ROS production and glutathione (GSH) levels, gene expression, caspase activity, and cytosolic Ca2+ concentration was examined. An initial 5-10-fold increase in ROS after glutamate addition is temporally correlated with GSH depletion. This early increase is followed by an explosive burst of ROS production to 200-400-fold above control values. The source of this burst is the mitochondrial electron transport chain, while only 5-10% of the maximum ROS production is caused by GSH depletion. Macromolecular synthesis inhibitors as well as Ac-YVAD-cmk, an interleukin 1beta-converting enzyme protease inhibitor, block the late burst of ROS production and protect HT22 cells from glutamate toxicity when added early in the death program. Inhibition of intracellular Ca2+ cycling and the influx of extracellular Ca2+ also blocks maximum ROS production and protects the cells. The conclusion is that GSH depletion is not sufficient to cause the maximal mitochondrial ROS production, and that there is an early requirement for protease activation, changes in gene expression, and a late requirement for Ca2+ mobilization.

Animals↗
PubMed1999

BCL-2 gene family and the regulation of programmed cell death.

The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing human follicular B cell lymphomas. BCL-2 proved to block programmed cell death rather than promote proliferation. Transgenic mice that overexpress Bcl-2 in the B cell lineage demonstrate extended cell survival and progress to high-grade lymphomas. Thus, BCL-2 initiated a new category of oncogenes, regulators of cell death. Bcl-2-deficient mice demonstrate fulminant apoptosis of lymphocytes, profound renal cell death and loss of melanocytes. BCL-2 protein duels with its counteracting twin, a partner known as BAX. When BAX is in excess, cells execute a death command; but, when BCL-2 dominates, the program is inhibited and cells survive. Bax-deficient mice display cellular hyperplasia, confirming its role as a proapoptotic molecule. An expanded family of BCL-2-related proteins shares homology clustered within four conserved regions termed BCL-2 homology 1 through 4 (BH1-4). These novel domains control the ability of these proteins to dimerize and function. An amphipathic alpha helix, BH3, is of particular importance for the proapoptotic family members. BID and BAD represent an evolving set of proapoptotic molecules, which bear sequence homology only at BH3. They appear to reside more proximal in the pathway serving as death ligands. BAD connects upstream signal transduction paths with the BCL-2 family, modulating this checkpoint for apoptosis. In the presence of survival factor interleukin-3, cells phosphorylate BAD on two serine residues. This inactivated BAD is held by the 14-3-3 protein, freeing BCL-XL and BCL-2 to promote survival. Activation of BAX results in the initiation of apoptosis. Downstream events in this program include mitochondrial dysfunction, as well as Caspase activation. The pro- and antiapoptotic BCL-2 family members represent central regulators in an evolutionarily conserved pathway of cell death. Aberrations in the BCL-2 family result in disordered homeostasis, a pathogenic event in diseases, including cancer.

Animals↗
PubMed2004

Time course of programmed cell death in Ciona intestinalis in relation to mitotic activity and MAPK signaling.

Programmed cell death (PCD) in the ascidian species Ciona intestinalis (Tunicata; Chordata) is investigated from early larvae to juvenile stages, by means of digoxigenin-based terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) technique. At first, PCD in the swimming larva affects trunk mesenchyme and central nervous system (CNS), then it participates extensively to metamorphosis, until it is restricted to developing organs of juveniles. Analysis of patterns of cell death and division in the larval CNS question old models on the genesis of the adult C. intestinalis brain. Upon performing immunochemical and functional assays for mitogen-activated protein kinase (MAPK) kinase kinase-1 (MEKK1), MAPK kinase 1/2 (MEK1/2), c-Jun NH2-terminal kinase (JNK), and dual phosphorylated extracellular regulated kinase 1/2 (dpERK1/2), the neurogenic competence of the larval brain appears to rely on a combinatorial regulation of PCD by the mitogen-activated protein kinase signaling cascade. These results show that, in tunicates, PCD consists of a multistep program implicated in growth and patterning with various roles.

Animals↗
PubMed1994

The role of programmed cell death (apoptosis) in thymic involution following sepsis.

OBJECTIVE: To test the hypothesis that thymic involution following peritoneal sepsis is secondary to thymocyte programmed cell death. DESIGN: We investigated the temporal response of thymic weight and thymic DNA fragmentation following peritoneal sepsis induced by cecal ligation and puncture in a rat model. We investigated the possible role of decreased interleukin (IL)-2 synthesis in the induction of apoptosis using rat thymocytes in primary culture. Finally, we studied IL-2 gene expression and IL-2 protein synthesis in phytohemagglutinin and IL-1 beta-treated thymocytes derived from the cecal ligation and puncture model of sepsis. RESULTS: We demonstrated that (1) there is a significant decrease in thymic weight and an increase in thymic DNA fragmentation with the characteristic apoptotic DNA "ladder" fragmentation pattern on agarose gel electrophoresis following peritoneal sepsis; (2) thymocytes in primary culture sustain a significant increase in thymocyte apoptosis following IL-2 withdrawal; and (3) peritoneal sepsis results in inhibition of phytohemagglutinin and IL-1 beta-induced thymocyte IL-2 messenger RNA accumulation and protein synthesis. CONCLUSIONS: Thymic involution following peritoneal sepsis is associated with increased thymocyte programmed cell death. Thymocyte apoptosis induced by sepsis may be the result, in part, of inhibition of IL-2 gene expression.

Animals↗