Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated apoptosis by nick end labeling and the expression of apoptosis-related proteins by immunohistochemistry in fetal development of human intrahepatic bile ducts and hepatocytes. During intrahepatic bile duct development, apoptosis was present at all stages, and its positive ratio was high in the remodeling ductal plate, moderate in the ductal plate, and relatively low in remodeled ducts. The cell proliferative activity as determined by proliferating cell nuclear antigen was also high in the remodeling ductal plate, and relatively low in the ductal plate and remodeled ducts. fas antigen and c-myc protein were constantly positive in the ductal plate, remodeling ductal plate and remodeled ducts. Bcl-2 protein was negative or faintly positive in the ductal plate and remodeling ductal plate, but was apparently positive in remodeled ducts. Lewisy as detected by the BM-1 antibody was present in the ductal plate, remodeling ductal plate, and remodeled ducts. p53 protein was not found in any cell types in the liver development. During hepatocyte development, many apoptotic and proliferating cell nuclear antigen-positive hepatocytes were noted. The developing hepatocytes expressed c-myc protein and fas antigen. Bcl-2 protein and Lewisy antigen were also weakly positive in the developing hepatocytes. These findings showed that balanced cell proliferation and apoptosis are involved in the normal development of intrahepatic bile ducts and hepatocytes, and suggest that c-myc protein, fas antigen, Bcl-2 protein, and Lewisy antigen modulate apoptosis of fetal intrahepatic biliary cells and hepatocytes, probably by stimulative (c-myc protein and fas and Lewisy antigens) or inhibitory (Bcl-2 protein) effects.
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PMID:Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development. 753 50

The ability of bcl-2 in target cells to block cell-mediated cytotoxicity by allospecific CTL was tested. The blocking effect was variable. Because killing by CTL involves two different pathways, degranulation (perforin plus granzymes) and fas, we examined the effect of bcl-2 on these pathways independently. Bcl-2 in target cells blocked apoptotic cell death induced either by cytotoxic granule extracts or by CTL killing under conditions in which the fas pathway is blocked. On the other hand, bcl-2 had no effect on target cell-killing either by Fas-specific mAb or by CTL capable of killing only via the fas pathway. These data suggest bcl-2 may block apoptotic lysis induced by perforin plus granzymes, but not apoptotic lysis induced via the fas pathway. Thus, any analysis of the effect of bcl-2 on apoptotic cell death in target cells killed by CTL must take into account the relative contributions of the degranulation vs fas pathways.
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PMID:Bcl-2 blocks degranulation but not fas-based cell-mediated cytotoxicity. 753 59

Cord blood lymphocytes are functionally immature and have deficient immune responses. In order to determine whether the process of programmed cell death is distinct between cord blood and peripheral blood lymphocytes, we analyzed the expression of fas and bax (apoptosis promoting genes) and bcl-2 and bcl-xL (apoptosis inhibiting genes) at protein or mRNA levels using flow cytometry and quantitative PCR methods, respectively. The susceptibility of T cell subsets from cord blood and adult peripheral blood to undergo apoptosis following restimulation with anti-CD3 or anti-Fas monoclonal antibodies was also studied. We observed that cord blood T cell subsets expressed lower levels of Fas and Bcl-2, a low bcl-2/bax ratio, and higher bcl-xL compared to peripheral blood. Additionally, upon primary stimulation with anti-CD3, cord blood T cell subsets were more resistant to apoptosis compared to peripheral blood. In contrast, rechallenge of previously stimulated lymphocytes with anti-CD3 monoclonal antibody triggered apoptosis in a larger proportion of T cells from cord blood as compared to peripheral blood, whereas the number of T cells undergoing anti-Fas-induced programmed cell death were lower in cord blood compared to peripheral blood.
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PMID:Programmed cell death (apoptosis) in cord blood lymphocytes. 904 87

Programmed cell death, an essential function in all cells, plays a central role in maintaining immune system homeostasis and controlling autoimmune reactions. Cell death may be an essential element in disseminated lupus erythematosus: defective cell death could lead to the development of autoreactive lymphocyte clones and degradation products of cell death could be implicated in autoimmunity induction and onset of renal lesions. Anomalies in programmed cell death have been demonstrated in murine models of lupus: mutations of the fas and fas-ligand genes, which play a known role in programmed cell death, produce the lpr and gld phenotypes associating lymphoproliferation and lupus. Transgenic mice which express Bcl-2 (the product of Bcl-2 inhibits programmed cell death) on B lymphocytes develop a lupus-type autoimmune disease. The role of these types of anomalies in human disease is not yet elucidated. However, cell death, via the degradation fragments of chromatin, could play a role in inducing antibody production and development of renal lesions. The anti-DNA antibodies, with characteristic antigen-induced immune response (clone expansion, class computation and somatic mutations) could be induced by nucleosomes released during cell death. Several arguments favor this mechanism including cation residues of histone nucleosomes which would bind to anionic residues of sulfate heparan and lead to deposit of autoantibodies in the glomerulus. The dual role of cell death is not really contradictory in autoimmune disease controlled by several independent genes, but would be compatible with several different genetic backgrounds.
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PMID:[Cell death and lupus]. 909 57

To understand the effects of ionizing radiation on thyroid cells, we investigated the role of p53 in mediating apoptosis and in DNA repair following in vivo and in vitro irradiation of thyroid cells. In vitro exposure of human thyroid cells to ionizing radiation of up to 5-8 Gy failed to induce apoptosis in primary cells. The same results were obtained when the thyroid gland was irradiated in the intact rat. To explore the mechanism of failure of the wild-type p53 in inducing apoptosis in thyroid cells, we investigated the expression of apoptosis-related genes, bax, bcl-2 and fas/APO-1 following irradiation or induction of temperature-sensitive p53. The expression of Bax, Bcl-2 and Fas/APO-1 in human primary cultured thyroid cells did not change after irradiation. To further confirm the results, we established a clonal cell line (tsFRO) in which a temperature sensitive p53 (Val138) expression vector was stably transfected to a thyroid carcinoma cell line lacking endogenous p53. Incubation of tsFRO cells at the permissive temperature for three days, however, did not induce apoptosis although G1 arrest was noted. Although enhanced expression of the bax mRNA level was observed, the expression of Bax, Bcl-2 and Fas/APO-1 protein did not change by shifting tsFRO cells to permissive temperature as well as irradiated primary cells. Furthermore, DNA end-jointing ability was examined by transfection of linearized luciferase plasmid into tsFRO cells. Increased luciferase activity occurred when the cells were cultured at the permissive temperature, indicating that the wild-type p53 enhances DNA end-jointing activity. Our results indicate that the wild-type p53 does not lead to apoptosis but facilitates DNA end-jointing in thyroid cells. These results may reflect specific responses in thyroid cells following irradiation.
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PMID:p53 induced by ionizing radiation mediates DNA end-jointing activity, but not apoptosis of thyroid cells. 912 41

Aging is associated with lymphopenia and progressive decline in T cell functions; however, the mechanisms underlying these defects are unclear. We analyzed the expression of genes promoting apoptosis (fas/fasL1 and bax) and those inhibiting apoptosis (bcl-2 and bcl-xL) in lymphocytes from aging and young subjects at the protein level, using flow cytometry/Western blotting, and at the mRNA level, using quantitative PCR. Susceptibility of T cell subsets to undergo anti-Fas-induced apoptosis was analyzed by propidium iodide staining, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, DNA fragmentation assay, and staining with Hoechst 33342 dye. An increased expression of Fas and Fas ligand and a decreased expression of Bcl-2 were observed in both CD4+ and CD8+ T cells from aging as compared with young controls. Increased Fas and decreased Bcl-2 expression were also found in memory cells of both CD4+ and CD8+ T cell subsets from aging. Bax expression was increased in lymphocytes from aging at both the protein and mRNA level. No significant difference was observed in Bcl-xL expression between aging and young; however, the ratio of Bax:Bcl-xL was increased in aging. An increased proportion of CD4+ and CD8+ T cell subsets from aging underwent apoptosis following anti-Fas Ab treatment as compared with CD4+ and CD8+ T cell subsets from young controls. These data suggest that increased apoptosis may be one of the mechanisms responsible for lymphopenia and T cell deficiency associated with human aging.
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PMID:Increased apoptosis of T cell subsets in aging humans: altered expression of Fas (CD95), Fas ligand, Bcl-2, and Bax. 946 19

The observations presented in this paper indicate that serum of Dalton's lymphoma (DL) bearing mice contained certain soluble factor(s) that augmented the induction of apoptosis in thymocytes in a time- and dose-dependent manner. DL-ascitic fluid and DL-conditioned medium could also induce apoptosis of thymocytes in vitro, though the magnitude of the same was consistently lower than that induced by serum of DL-bearing mice. It was observed that the interaction of FasL and TNFalpha with their respective receptors could trigger apoptosis in thymocytes. Elucidation of the signal transduction mechanism revealed involvement of protein tyrosine kinase, protein kinase C and ser/thr phosphatases with concomitant increase in the level of protein products of apoptosis associated genes p53, bax, bad, fas and fas ligand and cleavage of N-terminal 23 kDa fragment of Bcl-2 that exhibited Bax-like death effector properties. Further, we report, for the first time, the ability of thymosin alpha-1, an immunopotentiating thymic hormone, to antagonize apoptosis in thymocytes induced by factors present in serum of DL-bearing mice. The underlying mechanism of tumor serum induced apoptosis inhibition by thymosin alpha-1 was also analyzed. The signal transduction cascade evoked by thymosin alpha-1 involves activation of protein kinase C with a decrease in the level of protein products of proapoptotic genes like bax and bad and increase in the protein products of bcl-2 gene.
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PMID:Mechanism of thymocyte apoptosis induced by serum of tumor-bearing host: the molecular events involved and their inhibition by thymosin alpha-1. 1068 4

The expression of fas gene in glioma cells varies with growth stage. When insulin-elicited transient apoptosis of glioma cells was in progress, the expression of fas gene increased at both transcriptional and translational levels. In contrast, the expression of fas-L gene in glioma cells remained constant. Apoptosis occurred in the cells having high level of surface Fas protein. When the expression of Fas-L in U-373MG cells was suppressed by ribozyme, the insulin-elicited transient apoptosis vanished. Overexpression of Bcl-2 in U-373MG cells did not alter significantly the cell cycle progression and the expression of fas gene. However, these cells were resistant to insulin-trigged death. Therefore, insulin-elicited apoptosis involved Fas-related death signal, and which could be prevented by the protective effect of Bcl-2.
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PMID:Transient apoptosis elicited by insulin in serum-starved glioma cells involves Fas/Fas-L and Bcl-2. 1070 37

Neutrophils possess a very short lifespan, dying by apoptosis. HL-60 cells undergo apoptosis after neutrophil differentiation with dimethyl sulfoxide (DMSO). We have found that the onset of apoptosis in neutrophil-differentiating HL-60 cells correlates with the achievement of an apoptosis-related gene expression pattern similar to that of peripheral blood mature neutrophils. Using reverse transcriptase-polymerase chain reaction, cloning, and sequencing techniques, we have found that HL-60 cells express bak, bik, bax, bad, bcl-2, bcl-xL, bcl-w, bfl-1, fas, and caspases 1-4 and 7-10. After DMSO treatment, bak, bcl-w, bfl-1, fas, and caspases 1 and 9 were up-regulated, whereas bik, bcl-2, and caspases 2, 3, and 10 were down-regulated at different degrees, achieving mRNA expression levels that correlated with those detected in peripheral blood neutrophils. Caspase-2 mRNA and protein expression was drastically reduced after HL-60 cell differentiation, being absent in both HL-60-differentiated neutrophils and mature neutrophils, whereas caspase-3 and -10 mRNA and protein expression were diminished upon HL-60 cell differentiation until achieving the respective levels found in mature neutrophils. Bak and bfl-1 mRNA levels were largely increased during DMSO-induced differentiation of HL-60 cells, and these genes were the bcl-2 family members that were expressed most abundantly in mature neutrophils. Bcl-2 overexpression or caspase inhibition prevented differentiation-induced apoptosis in HL-60 cells, but not their differentiation capability. Neutrophil spontaneous apoptosis was also blocked by the caspase inhibitor z-Asp-2,6-dichlorobenzoyloxymethylketone. Peripheral blood neutrophils expressed bak, bad, bcl-w, bfl-1, fas, and caspases 1, 3, 4, and 7-10, but hardly expressed bcl-2, bcl-xL, bik, bax, and caspase-2. These results suggest that the above gene expression changes in neutrophil-differentiating HL-60 cells may play a role in the acquisition of the neutrophil apoptotic features.
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PMID:Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells. 1081 Oct 13

Growth factor deprivation-induced apoptosis plays an important role in several cellular systems. However, knowledge of the molecular mechanisms involved are restricted to a few murine models or tumor cell lines. Therefore, we aimed studying signaling pathways leading to apoptosis in activated human peripheral T cells after IL-2 withdrawal. Lymphoblasts from patients with CD 95 (Fas/APO-1)-deficiency revealed that functional CD95 was not required to induce apoptosis after IL-2 withdrawal. Moreover, apoptosis induction in response to various cytotoxic stimuli was found to be mediated in the absence of functional CD95 but was affirmatorily influenced by IL-2 signaling. Immunoblots showed no downregulation of Bcl-2 or Bcl-xL and no upregulation of Bax, whereas decreased mitochondrial membrane potential was readily measurable 24 h after cytokine deprivation. Tetrapeptide inhibitors showed limited efficacy in preventing apoptosis whereas the caspase inhibitor zVAD-FMK potently blocked induction of apoptosis. Cleavage of different fluorogenic substrates revealed multiple caspase enzyme activities in lymphoblasts, which were not negatively affected by the fas mutation. Starting at 8 h after IL-2 withdrawal, upregulation of active caspase-3 but not of caspase-8 could be detected. Taken together, our data argue for molecular mechanisms of cytokine deprivation-induced apoptosis in activated human lymphocytes independent of CD95.
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PMID:CD 95-independent mechanisms of IL-2 deprivation-induced apoptosis in activated human lymphocytes. 1082 77


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