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)

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.
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PMID:Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells. 793 79

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.
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PMID:Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. 855 Dec 26

Programmed cell death by apoptosis occurs in both fetal and maternal tissues during early pregnancy. To investigate a role for apoptosis at the maternal-fetal interface, we have immunolocalized the bcl-2 protein in formalin-fixed decidual and placental tissue collected from women undergoing surgical termination of pregnancy (n = 22), from women undergoing a sporadic miscarriage (n = 16) and from women with a history of recurrent pregnancy loss (more than three consecutive pregnancy losses; n = 22) undergoing a further miscarriage. In all three groups, bcl-2+ cells were found in aggregates and dispersed in the stroma, and immunoreactivity was observed in glandular epithelium. Double immunostaining revealed that a majority of stromal bcl-2+ cells were CD56+ large granular lymphocytes. A computerized image analysis revealed no significant differences in percentage area of bcl-2 or CD56+ immunostaining. Significantly more biopsies from the surgical termination group (4/10) had > 20% positive immunostaining for CD56 compared with 0% in the other two groups combined (0/20; P < 0.05). Bcl-2 immunoreactivity was observed in the villi syncytiotrophoblast, and staining intensity was consistently greater in the surgical termination group. The possible roles of bcl-2 at the maternal-fetal interface are discussed.
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PMID:The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies. 904 21

Expression of the Fas 'death receptor', Fas (CD95/APO-1) renders cells susceptible to programmed cell death ('apoptosis'), whereas Bcl-2 protects cells from apoptosis. Using fluorescence immunohistochemistry, we analysed Fas and Bcl-2 expression in muscle from five patients with polymyositis (PM), four patients with inclusion body myositis (IBM), three patients with dermatomyositis (DM), three patients with Duchenne muscular dystrophy (DMD) and three nonmyopathic controls. Fas (CD95) and Bcl-2 were not detected in control muscle, but expressed in muscle fibres and inflammatory cells in PM, IBM, DM and DMD. The proportion of Fas+ muscle fibres ranged from < 1 to 50%, and was higher in PM and IBM than in DM and DMD. On average, the Fas+ muscle fibres were smaller (median diameter, 10 microns; range, 7-32 microns) than the Fas- fibres (median, 36 microns; range, 10-60 microns). Less than 10% of the Fas+ muscle fibres co-expressed the regeneration marker CD56 (neural cell adhesion molecule N-CAM). In PM and IBM, the proportion of Fas+ muscle fibres was higher among fibres invaded or contacted by T cells than among fibres not contacted by T cells (P < 0.01). The proportion of Fas+ fibres co-expressing Bcl-2 was 76 +/- 16% in PM, 100% in IBM and 63 +/- 23% in DM. Fas and Bcl-2 expression was also noted in inflammatory cells in PM, IBM, DM and DMD. Using the terminal deoxytransferase-catalysed DNA nick end labelling technique for detection of nuclear DNA fragmentation, none of myonuclei, and < 0.1% of inflammatory cell nuclei, showed signs of apoptosis. Our results suggest that, although Fas expression confers susceptibility to Fas-mediated apoptosis, Fas-expressing muscle fibres and inflammatory cells are protected by the anti-apoptotic protein Bcl-2.
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PMID:Cytotoxic mechanisms in inflammatory myopathies. Co-expression of Fas and protective Bcl-2 in muscle fibres and inflammatory cells. 921 78

Bcl-2 is a major anti-apoptotic protein expressed in many normal and malignant cells. Recently, low to absent expression was reported in human natural killer (NK) cells cultured in serum-free media which could be induced with stem cell factor. We investigated the expression of bcl-2 protein of NK cells in normal blood donors and compared the bcl-2 expression in CD56+ NK cells with CD3+ T cells. To determine bcl-2 reactivity, a three-color flow-cytometric technique was used. CD56+ CD3- NK cells had an average bcl-2 expression of 83% compared with CD3+ T cells. CD56 and CD3 double positive T cells had an average content of 111% compared with all peripheral CD3+ T lymphocytes. When peripheral mononuclear cells were cultured with interleukin-2 (IL-2), bcl-2 could be upregulated by IL-2 in all cell populations studied. The induction of bcl-2 in these cell populations paralleled the induction in CD56- T lymphocytes cultured under identical conditions. The induction of bcl-2 by IL-2 was confirmed by Western blotting. The maximum induction of bcl-2 by IL-2 was observed at an IL-2 dose of 100-1,000 U/ml. Our data confirm the anti-apoptotic protein bcl-2 as an activation- or proliferation-associated marker of normal NK cells which can be induced by IL-2.
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PMID:Bcl-2 is expressed in human natural killer cells and is regulated by interleukin-2. 952 82

The effects of L1-Fc and CHL1-Fc fusion proteins on neuronal survival were investigated. Cerebellar granule neurons of mouse and hippocampal neurons of rat embryo undergo apoptosis when cultured in serum-free medium. Treatment with chimeric proteins containing the extracellular domains of the neural adhesion molecules L1 or CHL1 fused to the Fc region of human immunoglobulin significantly enhanced the survival of neurons. Compared to the control, the percentage of surviving neurons increased about 60% and 45% with L1 and CHL1 fusion proteins, respectively. A fusion protein containing the extracellular domain of NCAM had no effect on survival. The L1 and CHL1 fusion proteins were effective both in soluble form or when offered as a substrate, with the maximal effect at about 1 microg/mL. To explore the intracellular events related to the neuronal survival effects of L1-Fc fusion protein, Bcl-2 and c-Jun expression were analyzed by Western blotting. The level of Bcl-2 in cerebellar granule neurons was increased by treatment with L1-Fc at both 1 and 5 days of culture. The level of c-Jun was not significantly affected at the early time point and was reduced by L1-Fc fusion protein after long-term culture. The results demonstrate that the neural adhesion molecule L1 and its relative CHL1 are potential neuronal survival factors for neurons of the central nervous system. Bcl-2 may serve as one of the intracellular mediators of the neuronal survival effects of L1.
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PMID:Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1. 1002 83

Congenital atrichia is a form of total alopecia inherited in an autosomal recessive pattern. In individuals affected with this form of hair loss, hairs are typically absent from the scalp, and patients are nearly completely devoid of eyebrows, eyelashes, axillary and pubic hair, following shedding of the natural hair shortly after birth. We have recently linked this disorder to the chromosomal region 8p12, and cloned the human hairless gene, which resides within this interval. We have identified several mutations in the hairless gene in atrichia families from around the world. In hairless mice, the hair matrix cells appear to undergo a premature and massive apoptosis, together with a concomitant decline in Bcl-2 expression, a loss of NCAM positivity, and a disconnection with the overlying epithelial sheath essential for the movement of the dermal papilla. As a consequence, the hair bulb and dermal papilla remain stranded in the dermis, and indispensible messages between the dermal papilla and stem cells in the bulge are not transmitted, so no further hair growth occurs. These findings suggest that the hairless gene product may play a crucial role in maintaining the delicate balance between cell proliferation, differentiation and apoptosis in the hair follicle, as well as in the interfollicular epidermis.
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PMID:The molecular basis of congenital atrichia in humans and mice: mutations in the hairless gene. 1067 75

Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival.
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PMID:Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2. 1201 Oct 15

Allogeneic bone marrow transplantation (alloBMT) is the only curative therapy for chronic myelogenous leukemia (CML). This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI) producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma), and unstimulated (in vivo) lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR), of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2) on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.
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PMID:Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation. 1476 74

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.
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PMID:Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature. 1516 28


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