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)

Rat pregnancy is characterized by a progressive continuous induction of apoptosis in the maternal tissues lining the conceptus. Different cell types (decidual cells, giant cells, epithelial cells, etc.) undergo apoptosis at the different stages of development. We demonstrated here that, independently from their origin and stage of pregnancy, the dying cells were invariably characterized by the presence of 'tissue' transglutaminase (tTG) and negligible amounts of Bcl-2 proteins. This finding confirms the antithetic roles played by these two gene products within the apoptotic pathway. It is noteworthy that Bcl-2 was detected in decidual cells just after the implant; however, starting from day 9, its positive detection was reduced in the maternal tissues and appeared in the embryonal ones. The apoptotic nature of death was also suggested by the presence of a high phagocytic activity in the maternal involuting regions and by morphological observations showing that the tTG positive cell remnants displayed typical phenotypic features of apoptosis. The possibility that the cells lining the conceptus that die by apoptosis could be envisaged as an inert barrier between the maternal and fetal tissues is discussed.
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PMID:Immunohistochemical localization of tissue transglutaminase and Bcl-2 in rat uterine tissues during embryo implantation and post-partum involution. 791 42

Cell proliferation, the balance between mitosis and apoptosis is the result of the continuous integration of a number of different signal transduction pathways stimulated in a cell at any given point in its life. Neuroblastoma cells regulate the switch between mitosis and death, according both to intrinsic factors and extrinsic factors, such as growth factor withdrawal and action of the vitamin A derivative, retinoic acid. In this review, we describe the balance of some factors regulating growth and death of human neuroblastoma cells in vitro. These dynamic studies are necessarily-performed on cell lines, which offer controlled conditions enabling the disection of the complex stimuli mediating survival and growth (IGF, trk, BDNF) and death (transglutaminase, free radicals, Bcl-2). Although the conclusions drawn may therefore not be directly applicable to tumour cells in vivo, the results herein discussed are of sufficient significance to warrant in vivo relevance.
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PMID:Retinoids and the control of growth/death decisions in human neuroblastoma cell lines. 904 32

Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component of the food flavor turmeric (Curcuma longa) that exhibits anticarcinogenic properties in vivo. In vitro, it suppressed c-jun/Ap-1 and NF-kappaB activation and type 1 human immunodeficiency virus long-terminal repeat-directed gene expression. We examined the antiproliferative effects of curcumin against several breast tumor cell lines, including hormone-dependent and -independent and multidrug-resistant (MDR) lines. Cell growth inhibition was monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet dye uptake and flow cytometry. All the cell lines tested, including the MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory effect of curcumin was time- and dose-dependent, and correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was neither due to apoptosis nor to any significant change in the expression of apoptosis-related genes, including Bcl-2, p53, cyclin B and transglutaminase. Overall our results suggest that curcumin is a potent antiproliferative agent for breast tumor cells and may have potential as an anticancer agent.
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PMID:Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. 921 11

Keratinocyte differentiation and melanogenesis are two major cellular processes by which the epidermal compartment of the skin acquires its protective properties. Bcl-2; an oncoprotein involved in the regulation of apoptosis, has been shown to be expressed by keratinocytes and melanocytes. To determine whether Bcl-2 and Bax, a protein which heterodimerizes with Bcl-2, may control these epidermal functions, we investigated the expression of these two oncogenes in cultivated human keratinocytes and melanocytes from the same donors, respectively induced to differentiate and to produce melanin. As determined by cytometry, we observed that these two cell types constitutively express the two proto-oncogenes. Quantification of Bcl-2 antigen sites per cell showed that Bcl-2 expression is higher in keratinocytes than in melanocytes. An increase in transglutaminase activity, a marker of keratinocyte terminal differentiation initiating cornified envelope formation, was accompanied by a decrease in Bcl-2 levels without significant modification of Bax expression. In melanocyte cultures, stimulation of the dopa-oxidase pool, a key enzyme in melanin synthesis, paralleled Bcl-2 down-regulation and Bax up-regulation. This led us to conclude that the expression of these two oncogenes and their cellular ratio are closely involved in keratinocyte differentiation and melanogenesis.
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PMID:Expression of Bcl-2 and Bax in cultured normal human keratinocytes and melanocytes: relationship to differentiation and melanogenesis. 947 Sep 3

Villous trophoblast in the human placenta consists of a population of proliferating stem cells which differentiate and individually fuse into the syncytiotrophoblast. We studied the apoptotic cascade in this complex epithelial layer by immunohistochemical localization of Fas, FasL, Bcl-2, Mcl-1, pro-caspase-3 and caspase-3, T-cell-restricted intracellular antigen-related protein (TIAR), poly(ADP-ribose) polymerase (PARP), lamin B, topoisomerase IIalpha, and transglutaminase II in cryostat and paraffin-fixed tissue sections from normal human first-trimester and term placental villi. The relationship between the apoptotic cascade and syncytial fusion was studied by coincubation of intact villi with FITC-coupled annexin-V, to detect the phosphatidylserine flip, and propidium iodide, to detect plasma membrane permeability. The final events of the apoptotic cascade were studied by the TUNEL reaction and ultrastructural appearance of the trophoblast. The phosphatidylserine flip was identified in some of the villous cytotrophoblastic cells, but the presence of both Bcl-2 and Mcl-1 proteins presumably prevented continuation of the apoptotic cascade. The syncytiotrophoblast demonstrated heterogeneous findings, suggesting variable progression along the apoptotic cascade. In some areas Bcl-2 and Mcl-1 predominated, with preservation of the nuclear proteins PARP, lamin B, and topoisomerase IIalpha; in other areas, especially in and around syncytial sprouts, Bcl-2 and Mcl-1 were absent, accompanied by loss of nuclear proteins, presence of phosphatidylserine flip, and TUNEL positivity. These data suggest that the apoptotic cascade is initiated in the villous cytotrophoblast, which in turn promotes syncytial fusion. Donation of anti-apoptotic proteins into the syncytium, such as Bcl-2 and Mcl-1, focally inhibits further progression along this cascade. Completion of the apoptotic cascade takes place in and around syncytial sprouts, providing further evidence that these are the sites of trophoblast shedding into the maternal circulation.
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PMID:Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. 982 29

The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co-culture of murine or human DC with different tumor cell lines for 4-48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time- and dose-dependent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apoptosis involved regulation of Bcl-2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC-based immunotherapies for cancer and other immune diseases.
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PMID:Tumor's other immune targets: dendritic cells. 1044 78

Enhanced apoptosis characterizes several pathologies affecting human liver. This study sought to determine whether apoptosis is involved in the formation of fibrotic lesions occurring in hepatic disease. The expression of Bcl-2 was analysed, and of 'tissue' transglutaminase (tTG), a cross-linking enzyme which recent evidence suggests plays a role in the formation of fibrotic lesions in experimental settings. Regardless of the degree of liver injury, tTG abnormally accumulated in the liver cells adjacent to fibrotic tissue. Many cells showing DNA fragmentation and morphological features of apoptosis were also observed near fibrotic lesions. Bcl-2 was detected predominantly in infiltrating lymphocytes within the liver tissue. Marked staining for both tTG protein and chromatin was also observed in the acellular fibrotic tissue, which suggested an active release of intracellular macromolecules from the dying cells into the extracellular matrix. This study indicates that fibrogenesis in the liver is associated with the release of tTG from dying cells. By cross-linking extracellular matrix proteins, this enzyme might play a role in the formation of fibrotic lesions.
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PMID:'Tissue' transglutaminase release from apoptotic cells into extracellular matrix during human liver fibrogenesis. 1045 94

Treatment of the human promonocytic cell line U937 with all-trans-retinoic acid (RA) commits these cells to apoptosis, which can be triggered by simply increasing intracellular calcium levels by the ionophore A23187. RA treatment of U937 cells is characterized by a decrease in Bcl-2 and marked induction of "tissue" transglutaminase (tTG) gene expression. In this study, we show that the inhibition of tTG expression in U937 cells undergoing apoptosis prevents their death. In fact, U937 cell-derived clones transfected with the human tTG gene in the antisense orientation showed a pronounced decrease in apoptosis induced by several stimuli. These findings demonstrate that the Ca(2+)-dependent irreversible cross-linking of intracellular proteins catalyzed by tTG represents an important biochemical event in the gene-regulated cell death in monoblasts. In addition, our data indicate that the apoptotic program in promonocytic cells is strictly regulated by RA and that a key role is played by the free intracellular calcium concentration.
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PMID:Inhibition of "tissue" transglutaminase increases cell survival by preventing apoptosis. 1056 82

In thymocytes, peroxynitrite induces poly(ADP-ribose) synthetase (PARS) activation, which results in necrotic cell death. In the absence of PARS, however, peroxynitrite-treated thymocytes die by apoptosis. Because Bcl-2 has been reported to inhibit not only apoptotic but also some forms of necrotic cell death, here we have investigated how Bcl-2 regulates the peroxynitrite-induced apoptotic and necrotic cell death. We have found that Bcl-2 did not provide protection against peroxynitrite-induced necrotic death, as characterized by propidium iodide uptake, mitochondrial membrane potential decrease, secondary superoxide production, and cardiolipin loss. In the presence of a PARS inhibitor, peroxynitrite-treated thymocytes from Bcl-2 transgenic mice showed no caspase activation or DNA fragmentation and displayed smaller mitochondrial membrane potential decrease. These data show that Bcl-2 protects thymocytes from peroxynitrite-induced apoptosis at a step proximal to mitochondrial alterations but fails to prevent PARS-mediated necrotic cell death. Activation of tissue transglutaminase (tTG) occurs in various forms of apoptosis. Peroxynitrite did not induce transglutaminase activity in thymocytes and did not have a direct inhibitory effect on the purified tTG. Basal tTG was not different in Bcl-2 transgenic and wild type cells.
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PMID:BCL-2 protects peroxynitrite-treated thymocytes from poly(ADP-ribose) synthase (PARS)-independent apoptotic but not from PARS-mediated necrotic cell death. 1105 71

Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB- 1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p = 0.013). Irradiation caused the reduction of MIB-1+ (p = 0.0015), DO-7+ (p = 0.0043) and the increase of Bcl-2+ cells (p = 0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p = 0.0186) and no treatment (p = 0.0158), low ISNT scores (p = 0.0018) and high DO-1 scores (p = 0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-I and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.
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PMID:Distinct radiochemotherapy protocols differentially influence cellular proliferation and expression of p53 and Bcl-2 in glioblastoma multiforme relapses in vivo. 1108 75


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