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Showing papers on "Apoptosis published in 1990"


Journal ArticleDOI
22 Nov 1990-Nature
TL;DR: It is demonstrated that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k) being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.
Abstract: The t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein. Transgenic mice bearing a bcl-2 immunoglobulin minigene demonstrate a polyclonal expansion of resting yet responsive IgM-IgD B cells which display prolonged cell survival but no increase in cell cycling. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation. By using immunolocalization studies we now demonstrate that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k). Overexpression of Bcl-2 blocks the apoptotic death of a pro-B-lymphocyte cell line. Thus, Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.

3,773 citations


Journal ArticleDOI
04 Jan 1990-Nature
TL;DR: It is shown that the death of haemopoietic precursor cells on withdrawal of the relevant CSF is due to active cell death5, or apoptosis, indicating that CSFs promote cell survival by suppression of the process of apoptosis.
Abstract: The survival, differentiation, proliferation and development of haemopoietic precursor cells and the functional activity of mature blood cells are all influenced by colony stimulating factors (CSFs). As haemopoietic cells rapidly die in the absence of appropriate CSF, the promotion of cell survival mediated by CSFs, or growth factors, is fundamental to all the other effects exerted by these factors. This enhancement of cell survival is distinct from the stimulation of proliferation. Here we show that the death of haemopoietic precursor cells on withdrawal of the relevant CSF. is due to active cell death, or apoptosis, indicating that CSFs promote cell survival by suppression of the process of apoptosis. The existence of a positive control mechanism regulating precursor cell survival has important implications both for the regulation of normal haemopoiesis and for tumorigenesis.

956 citations


Journal ArticleDOI
TL;DR: Analysis of cell death induced by cisplatin in Chinese hamster ovary cell lines suggests that, irrespective of the primary site of action of a drug, cell death by most pharmacologic agents is mediated by activation of the signal transduction pathway for apoptosis.

895 citations


Journal ArticleDOI
11 Jan 1990-Nature
TL;DR: It is reported that macrophage recognition of apoptotic cells (both neutrophils and lymphocytes) is mediated by the vitronectin receptor, a heterodimer belonging to the β3 or cytoadhesin family of the integrins.
Abstract: PHAGOCYTE recognition of cells that have undergone apoptosis (programmed cell death) is an event of broad biological significance. Characterized by endogenous endonuclease activation1, which results in chromatin fragmentation and nuclear condensation2, apoptosis leads to swift ingestion of intact but 'senescent' or 'unwanted' cells by phagocytes in processes as diverse as the physiological involution of organs, the remodelling of embryonic tissues, and metamorphosis3. The cell-surface mechanisms by which macrophages recognize apoptotic cells as 'senescent-self' have remained obscure. Here we report that macrophage recognition of apoptotic cells (both neutrophils and lymphocytes) is mediated by the vitronectin receptor, a heterodimer belonging to the β3 or cytoadhesin family of the integrins4–9. Previously, the functions of the vitronectin receptor were believed to be limited to cell anchorage10–12, but our findings indicate that the receptor has a novel and direct role in self–senescent-self intercellular recognition leading to macrophage phagocytosis of cells undergoing apoptosis.

851 citations


Journal ArticleDOI
20 Apr 1990-Science
TL;DR: DNA cleavage is a major component of normal erythropoiesis, and ERYthropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells.
Abstract: The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells.

832 citations


Journal Article
TL;DR: The results suggest that androgen-dependent human prostatic cancer cells, like normal prostatic cells, retain the ability to inhibit proliferation and to activate programmed cell death in response to androgen ablation.
Abstract: To study the mechanism of regression of human prostatic cancer following androgen ablation, the androgen-responsive PC-82 human prostatic adenocarcinoma xenograft was used as a model system Castration of male nude mice bearing PC-82 xenografts results in a 50% tumor regression by 2 wk following androgen ablation This regression is due to a sequence of biochemical and morphological events that results in both the cessation of cell proliferation and activation of programmed death or apoptosis of the androgen-dependent prostatic cancer cells Associated with this response are an enhanced expression of the transforming growth factor beta 1 gene, a potent inhibitor of cell proliferation, and testosterone-repressed prostatic message 2 (designated TRPM-2), a programmed cell death-associated gene Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that preceded the dramatic reduction in tumor volume following androgen ablation These results suggest that androgen-dependent human prostatic cancer cells, like normal prostatic cells, retain the ability to inhibit proliferation and to activate programmed cell death in response to androgen ablation Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even androgen-independent human prostatic cancer

499 citations


Journal Article
TL;DR: The results suggest that certain dividing cell populations do not require RNA or protein synthesis to undergo apoptosis and further, that continuous transcription and translation of some regulatory protein(s) may be required to maintain control over the apoptotic "machinery" of such cells.
Abstract: Apoptosis is regarded as a suicidal cell response since the dying cell appears to be an active participant. Previous studies have shown that apoptosis of various murine cell types, induced by a variety of stimuli, required RNA and/or protein synthesis. However, when human promyelocytic leukemia HL-60 cells were induced to undergo apoptosis by treatment with the calcium ionophore A23187 or microtubule-disrupting agents, in the presence of inhibitors of macromolecular synthesis, apoptosis of these cells was neither abrogated nor delayed. Furthermore, the presence of either cycloheximide, an inhibitor of protein synthesis, or actinomycin D, an RNA synthesis inhibitor, alone was found to induce large scale apoptosis of these cells. Apoptosis in these cells was characterized by cell and chromatin condensation followed by nuclear and DNA fragmentation. In common with many other studies, this DNA fragmentation was found to have an approximately 200-bp multiple pattern, which is consistent with the activation of an endogenous endonuclease which cleaves at internucleosomal sites. Calcium-dependent endonuclease activity of this type was also detected in the isolated nuclei of untreated HL-60 cells. The morphologic and biochemical changes characteristic of apoptosis were found to precede cell death, as measured by trypan blue uptake and were completely distinct from death caused by toxic stimuli such as azide, ethanol, or heat treatment. Similar experiments with six other human cell lines confirmed that this phenomenon was not peculiar to the HL-60 cell line. These results suggest that certain dividing cell populations do not require RNA or protein synthesis to undergo apoptosis and further, that continuous transcription and translation of some regulatory protein(s) may be required to maintain control over the apoptotic "machinery" of such cells.

496 citations


Journal ArticleDOI
TL;DR: A method to determine the duration of apoptosis in normal and putative preneoplastic tissue of the liver is described and may provide data for quantitative cancer risk assessment from mathematical models of carcinogenesis.
Abstract: Apoptosis is a form of cell death involved in the regulation of cell number in various organs and tumors. Quantitative determination of cell loss through apoptosis in histological sections requires, in addition to counts of apoptotic cells, information on the duration of the histologically visible stages of apoptosis. Here we describe a method to determine the duration of apoptosis in (i) normal and (ii) putative preneoplastic tissue of the liver. (i) Female rats were treated with high doses of the hepatomitogen cyproterone acetate (CPA) to induce liver hyperplasia. After stopping CPA treatment, the hyperplasia partially regressed and excessive hepatocytes were eliminated by apoptosis. CPA was given to block the initiation of apoptosis, and thereafter the time course of elimination of apoptotic cell residues (apoptotic bodies, ABs) from the liver was studied. The mean duration of the histological stages of apoptosis was found to be approximately 3 h. (ii) Phenotypically altered cell foci in rat liver were produced by a single dose of N-nitrosomorpholine and subsequent promotion for 39 weeks with phenobarbital (PB). PB was withdrawn to stop foci growth and to stimulate apoptosis. Then rats were retreated with PB to block initiation of apoptosis in foci. The results indicate that the majority of apoptotic bodies in foci disappeared within 4 h after PB, suggesting that the stages of apoptosis are as short in foci as in normal liver. Finally a simple formula is given to calculate the cell loss rate by apoptosis. The method presented may provide data for quantitative cancer risk assessment from mathematical models of carcinogenesis.

468 citations


Journal ArticleDOI
TL;DR: The slow cell death reported here appears to occur at the G2/M transition and may involve events that normally occur at this stage of the cell cycle, demonstrating the importance of DNA degradation as an early and possibly essential step in cell death.
Abstract: DNA is the accepted target for cisplatin, but recent evidence has shed doubt on DNA synthesis as the critical process. L1210/0 cells incubated for 2 hours with cisplatin progress to the G2 phase of the cell cycle and are arrested there for several days. They then either progress in the cell cycle or die. In cells that eventually die, total transcription, polyadenylated [poly(A)+] RNA synthesis, and protein synthesis were markedly inhibited only after 48 hours. Nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) levels decreased after 3 days. Cell membrane integrity was lost after 4 days. These results demonstrate that cells can be lethally damaged, yet continue to undergo apparently normal metabolic activities for several days. In a previous study, DNA double-strand breaks were detected after 1 day. We now show that by 2 days, breaks are visible as fragmentation in the nucleosome spacer regions of chromatin. This type of damage is consistent with cell death occurring by the process of apoptosis. Cell shrinkage and morphology were also consistent with this type of cell death. The slow cell death reported here appears to occur at the G2/M transition and may involve events that normally occur at this stage of the cell cycle. These results demonstrate the importance of DNA degradation as an early and possibly essential step in cell death.

453 citations


Eastman A1
01 Aug 1990
TL;DR: In this paper, the authors show that the effects of cisplatin-induced cell death are reminiscent of apoptosis or programmed cell death, suggesting that these agents may all interact with the same signal transduction pathway leading to cell death.
Abstract: The anticancer drug cisplatin exerts its action as a consequence of interaction with DNA. Cell cycle progression facilitates sensitivity to the drug, but inhibition of DNA synthesis is not necessarily the critical step. Lethally damaged cells can progress to and arrest for several days in the G2 phase of the cell cycle before dying. Certain features of cisplatin-induced cell death, such as chromatin condensation and the activation of a DNA endonuclease, are reminiscent of apoptosis, or programmed cell death. Many other anticancer drugs produce the same phenotypic effects, suggesting that these agents may all interact with the same signal transduction pathway leading to cell death.

350 citations


Journal ArticleDOI
TL;DR: It is suggested that apoptosis following heating may be triggered either by a limited increase in cytosolic calcium levels resulting from mild membrane changes or by DNA damage, and necrosis, on the other hand, is likely to be a consequence of severe membrane disruption.
Abstract: SummaryThe pathogenesis of heat-induced cell death is controversial. Categorizing the death occurring after various heat loads as either apoptosis or necrosis might help to elucidate this problem, since it has been shown that these two processes differ in their mode of initiation as well as in their morphological and biochemical features. Log-phase cultures of mastocytoma P-815 × 2·1 were heated at temperatures ranging from 42 to 47°C for 30 min. After 42°C heating a slight increase in apoptosis was observed morphologically. However, after heating at 43, 43.5 and 44°C, there was marked enhancement of apoptosis, and electrophoresis of DNA showed characteristic internucleosomal cleavage. With heating at 45°C both apoptosis and necrosis were enhanced, whereas at 46 and 47°C only necrosis was produced. DNA extracted from the 46 and 47°C cultures showed virtually no degradation, which contrasts with the random DNA breakdown observed in necrosis produced by other types of injury; lysosomal enzymes released duri...

Journal ArticleDOI
TL;DR: Apoptosis is induced in the terminally differentiated cells of hormone-dependent tissues, such as the prostate and mammary gland in the absence of the appropriate trophic hormones, resulting in the regression of the tissue.
Abstract: In higher organisms homeostatic control of cell number is thought to be the result of the dynamic balance between cell proliferation and cell death. While the process of proliferation has received a great deal of attention over the past 20 years, much less emphasis has been placed on the biochemical events that occur before and during cell death. In higher organisms cell death can be classified into one of three different categories: necrosis, which occurs as a result of massive tissue damage; terminal differentiation of specialized tissues such as the skin, intestine, and red blood cells; and apoptosis, which is a process of active cellular selfdestruction that requires the expression of a number of genes. The latter process was originally recognized and described by Wyllie who coined the term "apoptosis" to describe the sequence of events that lead to cell death in a variety of different systems (Kerr et al., Br. J . Cancer, 26, 239-257, 1972), specifically to distinguish this form of cell death from necrosis. Apoptosis is induced in the terminally differentiated cells of hormone-dependent tissues, such as the prostate and mammary gland in the absence of the appropriate trophic hormones, resulting in the regression of the tissue. In other tissues apoptosis can be induced by positive modulators, such as Mullerian duct inhibiting substance (MIS) in the Mullerian ducts, tumor necrosis factor (TNF) in adipocytes, and a variety of cell lines and glucocorticoids in lymphocytes and thymocytes. It can also be induced in cells that retain their proliferative potential (such as hepatocytes) to maintain homeostasis of cell numbers in organs such as the liver. In both proliferating and nonproliferating systems, apoptosis requires specific gene transcription and protein synthesis in the affected cell prior to death, although the biochemical sequence of events may vary slightly from one tissue to another.


Journal Article
TL;DR: In this paper, an increase in the cAMP level by independent mechanisms was found to stimulate DNA fragmentation, characteristic of a suicide program known as apoptosis, in isolated thymocytes.
Abstract: Increases in the cAMP level are often inhibitory in mature T lymphocytes and may be involved in the development of tolerance to self Ag. In this report, agents inducing an increase in the cAMP level by independent mechanisms were found to stimulate DNA fragmentation, characteristic of a suicide program known as apoptosis, in isolated thymocytes. Data obtained with cAMP analogs known to act synergistically to stimulate protein kinase A suggested that the latter directly mediated endonuclease activation. Agents previously shown to stimulate protein kinase C and to inhibit Ca2(+)-dependent, TCR-mediated thymocyte apoptosis, including IL-1, also blocked both DNA fragmentation and cell death in response to cAMP, suggesting interactions ("cross-talk") between the two protein kinase systems. As it has been proposed that apoptosis mediates negative cell selection in the thymus, our results indicate that cAMP may play a role in the development of functional mature T lymphocytes.

Journal ArticleDOI
TL;DR: It is shown that anti‐γ antibodies induce DNA cleavage into oligonucleosomal fragments characteristic of programed cell death (apoptosis) in both cell lines, although WEHI‐231 cells are less susceptible than CH31, indicating that these lymphomas afford a potentially interesting model to study the mechanisms of programing cell death induced by ligation of the antigen receptors on normal B cells.
Abstract: WEHI-231 and CH31 are phenotypically immature sIgM+ murine B cell lymphomas whose growth is inhibited by anti-immunoglobulin (Ig) antibodies. These lines have therefore been used as models for studying the role of surface Ig receptors in the induction of B cell tolerance. We show here that anti-mu antibodies induce DNA cleavage into oligonucleosomal fragments characteristic of programmed cell death (apoptosis) in both cell lines, although WEHI-231 cells are less susceptible than CH31. This effect was reversed by lipopolysaccharide, in agreement with the known effects of lipopolysaccharide on anti-Ig-induced growth inhibition. These results therefore indicate that these lymphomas afford a potentially interesting model to study the mechanisms of programmed cell death induced by ligation of the antigen receptors on normal B cells.

Journal ArticleDOI
TL;DR: It is shown that anti‐mIg treatment causes DNA fragmentation (apoptosis) in immature B lymphocytes such as WEHI‐231 cells, and co‐treatment with the protein kinase C activator phorbol 12‐myristate 13‐acetate prevents apoptosis induced by anti‐ mIg.
Abstract: Anti-membrane immunoglobulin (anti-mIg) antibodies exert inhibitory effects in immature B lymphocytes such as WEHI-231 cells. We show here that anti-mIg treatment causes DNA fragmentation (apoptosis) in these cells. We also report that co-treatment with the protein kinase C activator phorbol 12-myristate 13-acetate prevents apoptosis induced by anti-mIg. These results are in agreement with our initial proposal that sensitivity to the toxic effects of anti-mIg reflects, at least partially, altered signal transduction in immature B lymphocytes. Variations in signal transduction pathways during B lymphocyte ontogeny may, therefore, play a critical role in determining whether B cells should be activated or inhibited via their mIg.

Journal Article
TL;DR: Apoptosis is an energy requiring process requiring intact energy generating systems, unlike that of necrosis, and is the mechanism by which cytotoxic T cells kill tumour target cells; it may also be the mechanism which accounts for the high loss of cells in growing tumour masses.
Abstract: Cell death can occur by two possible mechanisms, necrosis or apoptosis. Necrosis is the classically recognised form of cell death and is characterised by high amplitude swelling of the mitochondria, nuclear flocculation and uncontrolled cell lysis. Tissue necrosis is normally seen following severe trauma to cells. The alternative form of cell death is via a programmed sequence of events and is termed apoptosis. Apoptosis occurs under a variety of physiological conditions and cells dying by this process undergo cytoplasmic and nuclear condensation, coupled with cleavage of the cell's DNA into nucleosome size fragments. DNA cleavage is due to the activation of a specific endogenous endonuclease. The cell finally fragments into apoptotic bodies which are engulfed by neighbouring cells and degraded. Apoptosis is an energy requiring process requiring intact energy generating systems, unlike that of necrosis. In relation to malignant disease, apoptosis is the mechanism by which cytotoxic T cells kill tumour target cells; it may also be the mechanism which accounts for the high loss of cells in growing tumour masses. Extensive apoptosis is seen in regressing tumours and also in those treated with chemotherapeutic agents. This form of death may require the activation of specific death genes, although in view of work carried out in this and other laboratories, demonstrating that inhibitors of both protein and RNA synthesis will readily induce apoptosis, this may not be universal. Finally, apoptosis has far reaching implications for the treatment of malignant disease, since only by understanding how cells die will be able to develop more effective means of killing them.

Journal ArticleDOI
TL;DR: An immortalized interleukin‐3 (IL‐3)‐dependent progenitor cell line, BAF‐3, undergoes programmed cell death (apoptosis) when deprived of IL‐ 3, characterized by an early degradation of DNA into oligonucleosome‐length fragments that precedes by several hours the loss of cell viability.
Abstract: An immortalized interleukin-3 (IL-3)-dependent progenitor cell line, BAF-3, undergoes programmed cell death (apoptosis) when deprived of IL-3. This program is characterized by an early degradation of DNA into oligonucleosome-length fragments that precedes by several hours the loss of cell viability. In the absence of IL-3, DNA fragmentation and cell death can be prevented by the calcium ionophores A23187 (1 microM) and ionomycin (0.5 microM). This addition of calcium ionophore maintains cell viability while reversibly arresting the cell cycle. Apoptosis by growth factor deprivation is also a mechanism of cell elimination in bone marrow cells removed from the stromal micro-environment, as DNA fragmentation and cell death was shown to take place in primary cultures of IL-3-responsive bone marrow cells after IL-3 removal.

Journal Article
TL;DR: It is demonstrated that activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels, which indicate that AICD proceeds via apoptosis, or programmed cell death.
Abstract: Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs. In addition to the morphologic changes, a significant portion of genomic DNA is broken at an interval of approximately 200 bp, producing a ladder of oligonucleosome-sized fragments after gel electrophoresis. Taken together, these observations indicate that AICD proceeds via apoptosis, or programmed cell death. This is additionally supported by the observation that AICD-associated phenomena are at least partially inhibited by cycloheximide or actinomycin D. Curiously, AICD and its associated DNA fragmentation are completely inhibited by aurintricarboxylic acid, a known nuclease inhibitor. The possible relationship between AICD in vitro, and the negative selection process (wherein selection may proceed via AICD of developing, autoreactive thymocytes) is discussed.

Journal ArticleDOI
TL;DR: The results indicate that protein synthesis is not required for induction of apoptosis in macrophages or T blasts by gliotoxin, and the effects of actinomycin D and the protein synthesis inhibitor cycloheximide on apoptosis induced bygliotoxin are studied.

Journal ArticleDOI
TL;DR: Results are consistent with a greater susceptibility of thymocytes to tributyltin and provide a basis for understanding its selective immunotoxicity in vivo.

Journal ArticleDOI
TL;DR: Induction of apoptosis may be a possible therapeutic tool in HTLV-I-associated malignant disorders.

Journal ArticleDOI
TL;DR: The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death.
Abstract: The cell-free supernatants of normal spleen and thymus lymphocytes in short-term culture release low molecular weight (LMW) DNA protein molecules that have an immunoproliferative effect (polyclonal B cell activation) in vitro. We have determined that the protein-LMW DNA complexes responsible for these effects are nucleosomal constituents of chromatin, since the mitogenically active fractions of these cell-free supernatants contain the constituents of core histones (H3, H2A, H2B, H4) together with LMW DNA (140-180 bp), and since the immunoproliferative effects of these cell-free supernatants could be mimicked by various other nucleoprotein preparations (including calf thymus and chicken erythrocyte nucleosomes). The spontaneous cellular release of cleaved chromatin constituents in vitro can be attributed to a form of programmed cell death termed apoptosis, since the cultured spleen cells exhibited (a) morphologic evidence consistent with this process by electron microscopy, and (b) evidence of intracellular cleavage of chromatin which, like apoptosis, could be blocked with ZnSO4. This resulted in inhibition of the extracellular release of nucleosomal constituents as well as the immunoproliferative effects of the cell-free supernatants. The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death. In pathological states, this could result in abnormal polyclonal B cell proliferation and autoantibody formation.

Journal Article
TL;DR: It is suggested that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.
Abstract: In recent years, several studies have confirmed the clonal elimination of thymocytes with receptors that recognize Ag and MHC molecules present on the membrane of thymic stromal cells, a process that may be relevant to the establishment of self-tolerance. In our work, we show that anti-CD3 treatment of single positive CD4+ or CD8+ human medullary thymocytes (obtained by anti-CD1a plus C) induces their apoptotic death. Some events commonly associated with the early steps of normal activation (IL-2R expression, increase in cytoplasmic Ca2+) are also induced after anti-CD3 treatment. Nevertheless, IL-2 is not secreted by these activated cells. The addition of exogenous IL-2 inhibits the apoptosis induced by anti-CD3. We suggest that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.

Journal ArticleDOI
TL;DR: It is suggested that calcium influx could act at the microtubule level in efTftctino annntnsis, since microtubules are known to be highly sensitive to intracellular calcium fluctuations.
Abstract: . Terminally differentiated HL-60 cells undergoing programmed cell death (apoptosis) in culture were found to have a disrupted microtubular network. Treatment of undifferentiated HL-60 cells with microtubule-disrupting agents alone was found to induce apoptosis en masse in these cells. In contrast, disruption of microfilaments did not induce apoptosis; instead these cells underwent necrosis, the pathological mode of cell death. Apoptosis in response to microtubule disruption in HL-60 cells was characterized by cell shape changes, nuclear condensation followed by fragmentation and the separation of the cell into numerous intact fragments, termed apoptotic bodies. Apoptosis of these cells was further confirmed by DNA analysis, which demonstrated the activation of an endogenous endonuclease which cleaved the DNA of these cells into oligonucleosomal fragments. Microtubule disrupting agents were found to exert these effects over a wide range of doses. Apoptosis was also inducible in HL-60 cells, in a dose-dependant manner, by the calcium ionophore A23187. Since microtubules are known to be highly sensitive to intracellular calcium fluctuations, this suggests that calcium influx could act at the microtubule level in efTftctino annntnsis

Journal ArticleDOI
TL;DR: It is indicated that cold shock‐induced DNA fragmentation in McCoy's cells is dependent on a sustained Ca2+ increase, and sensitivity to the process appears to be regulated by the status of protein kinase C.

Journal ArticleDOI
TL;DR: The results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.

Journal ArticleDOI
TL;DR: The results suggest that apoptosis represents a new manifestation of cell injury after brief exposure to 0-6 degrees C hypothermia, and the amount of cell killing was dependent on the duration of hypotheria.

Journal ArticleDOI
TL;DR: ’ Erythroid progenitor cells in the bone marrow develop into reticulocytes in response to EPO, but the mechanism by which EPO controls this development is unknown, and EPO appears to act by maintaining cellular viability.

Journal ArticleDOI
TL;DR: The inhibition of apoptosis induced by ETP compounds by Zn2+ appears to be due to direct inhibition of oxidative damage to plasmid DNA in vitro by inhibiting auto-oxidation of the reduced ETP compound because of the looseness of the interaction.