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)

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and further processed for apoptosis detection. The highly characteristic DNA cleavage into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA strand breaks and the typical ultrastructural features of apoptosis were evident in dendritic cells exposed to the drug. More importantly, we demonstrated that granulocyte-macrophage colony-stimulating factor protects dendritic cells not only from apoptosis induced by the exogenous compound but also from spontaneous apoptosis. Western blot analysis revealed that this protection was tightly correlated with the activation of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of dendritic cells will be advantageous for the generation of new insights in immunotherapy.
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PMID:Granulocyte-macrophage colony-stimulating factor protects dendritic cells from liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a Bcl-2-mediated pathway. 1006 72

Analyses of apoptosis and of the apoptosis regulatory proteins Bcl-2, Bax, Bcl-X, and Bad were done in 95 nontumorous and neoplastic pituitary tissues by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL), immunohistochemistry, and Western blotting. The apoptotic index was relatively low in all groups but was at least fourfold higher in pituitary carcinomas compared with any other groups. Pituitaries from pregnant and postpartum women had a fivefold higher apoptotic index compared with matched controls from nonpregnant females. Preoperative treatment of adenomas with octreotide or dopamine agonists did not change the apoptotic index significantly. The lowest levels of Bcl-2, Bax, and Bcl-X expression were in pituitary carcinomas as detected by immunostaining. An immortalized human pituitary adenoma cell line, HP75, developed in our laboratory using a replication-defective recombinant human adenovirus with an early large T-antigen, had a much higher level of apoptosis than nontumorous and neoplastic pituitaries. Treatment with transforming growth factor (TGF)-beta1 and protein kinase C (PKC) inhibitors increased apoptosis in this cell line. Analysis of the Bcl-2 family of proteins after treatment with TGF-beta1 and PKC inhibitors showed a 20% to 30% decrease in Bcl-X in the treated groups compared with controls. These results, which represent the first study of apoptosis in pituitaries from pregnant and postpartum cases and in pituitary carcinomas, indicate that 1) the apoptotic rate is low in nontumorous and neoplastic pituitary tissues but is relatively higher in pituitary carcinomas, 2) there are alterations in the expression of the Bcl-2 family of proteins in pituitary neoplasms with a decrease in Bcl-2 expression in pituitary carcinomas that may contribute to pituitary tumor pathogenesis and/or proliferation, and 3) cultured pituitary tumor cells respond to TGF-beta1 and PKC inhibitors by undergoing apoptotic cell death.
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PMID:Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl-2 family of proteins. 1007 54

Perinatal brain damages are caused mainly by circulation insufficiency due to intrauterine or birth asphyxia. Hypoxic-ischemic encephalopathy (HIE) and pontosubicular neuronal necrosis (PSN) are typical perinatal ischemic diseases. We investigated the expression of apoptosis in these diseases, using TdT-mediated dUTP nick end labeling (TUNEL) method and immunohistochemistry with Bcl-2, Bcl-x, Bak and caspase 3 (CPP 32). In HIE, Purkinje cells showed overexpression of Bcl-2 and CPP 32, and some karyorrhectic cells were positive for TUNEL. In PSN, neurons of the pontine nuclei showed overexpression of Bcl-x and CPP 32, and most karyorrhectic neurons were positive for TUNEL. Immature neurons were susceptible to these changes. Apoptosis may play an important role in the pathomechanism of perinatal ischemic brain damages.
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PMID:[Perinatal ischemic brain damages and apoptosis]. 1019 36

A glomangiosarcoma arose in a benign glomus tumour. The histological and immunohistochemical characteristics of the tumour were investigated. Apoptotic cells were identified by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling (TUNEL). The proportion of apoptotic cells was found to be low and TUNEL positive nuclei were present in the benign part of the tumour. Bcl-2 protein, an inhibitor of apoptosis, was strongly expressed in the glomangiosarcoma with only weak staining in the benign area. The proliferation index of the glomangiosarcoma was almost 10-fold higher than that of the benign glomus tumour. Numerous nuclei in the glomangiosarcoma were intensely stained for the tumour suppressor protein p53. The results of the this study may contribute to an understanding of the molecular basis of malignant transformation in benign glomus tumours.
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PMID:Histochemical investigation into the molecular mechanisms of malignant transformation in a benign glomus tumour. 1019 35

Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to regress tumors in mice. In this study, we have analyzed the mechanism of endostatin action on endothelial cells and nonendothelial cells. Endostatin treatment of cow pulmonary artery endothelial cells caused apoptosis, as demonstrated by three methods, annexin V-fluorescein isothiocyanate staining, caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay. Moreover, addition of endostatin led to a marked reduction of the Bcl-2 and Bcl-XL anti-apoptotic protein, whereas Bax protein levels were unaffected. These effects were not seen in several nonendothelial cells. Collectively, these findings provide important mechanistic insight into endostatin action.
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PMID:Endostatin induces endothelial cell apoptosis. 1020 87

A gradual loss of cells occurs within the human trabecular meshwork during normal aging and appears to be increased in patients with primary open-angle glaucoma. The exact mechanism by which cells are lost in either condition is not known, however phagocytosis, cell migration and cell death have been suggested. Apoptosis is one method by which cell death can occur. We have examined the modulators for apoptosis within the human trabecular meshwork using both cell lines and ex-vivo dissected trabecular meshwork tissues obtained from normal donors. Using RT-PCR it was shown that mRNA for several modulators of apoptosis (Fas, Bcl-2, Bcl-xl, Bax, and ICE) are expressed by both cell lines and ex-vivo tissues. Apoptosis was stimulated to occur by treating cell lines with a monoclonal antibody (IgM) to Fas. Apoptosis was verified via morphological changes to the cells, transferase-mediated dUTP nick-end labeling TUNEL Immunofluorescence, and DNA laddering. Control cells exposed to IgM did not undergo apoptosis. These results represent the first report of apoptosis modulators within the human trabecular meshwork and demonstrate that human trabecular meshwork cells can be stimulated to undergo apoptosis via the Fas/FasL pathway.
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PMID:Fas-activated apoptosis and apoptosis mediators in human trabecular meshwork cells. 1032 72

The purpose of this study was to assess the role of apoptosis and cell cycle arrest in the trophoblast during early gestation by determining the location of apoptotic cells and examining the expression of Bcl-2 and p21. Using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method on human chorionic villi, a cluster of apoptotic nuclei was demonstrated in perivillous fibrin-type fibrinoid, but no apoptotic changes were identified in the syncytiotrophoblast or in other subtypes of the trophoblast. The syncytiotrophoblast was diffusely positive for Bcl-2, but fibrin-type fibrinoid was negative for Bcl-2. Hence, there was an inverse relationship between apoptosis and Bcl-2 expression in both fibrin-type fibrinoid and syncytiotrophoblast. Expression of p21 was present to some extent in the syncytiotrophoblast, but not in fibrin-type fibrinoid. These results suggest that Bcl-2 may play an important role in preventing apoptosis in the syncytiotrophoblast; this may be necessary to prevent any DNA degradation from being spread to other nuclei in a multinuclear cell like the syncytiotrophoblast.
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PMID:Inverse relationship between apoptosis and Bcl-2 expression in syncytiotrophoblast and fibrin-type fibrinoid in early gestation. 1033 59

Preeclampsia is a serious pregnancy complication diagnosed by signs of widespread maternal endothelial dysfunction. In normal pregnancy, a subpopulation of placental cytotrophoblast stem cells executes an unusual differentiation program that leads to invasion of the uterus and its vasculature. This process attaches the conceptus to the uterine wall and starts the flow of maternal blood to the placenta. Preeclampsia is associated with abnormal cytotrophoblast differentiation, shallow invasion, and decreased blood flow to the placenta. To determine whether abnormal differentiation and/or hypoxia leads to cytotrophoblast apoptosis, we used the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) method to label DNA strand breaks in tissue sections of the placenta and the uterine wall to which it attaches. Control samples (n = 9) showed almost no apoptosis, but in samples from patients with preeclampsia, 15-50% of the cytotrophoblasts that invaded the uterine wall were labeled (8/9 samples). These same cells failed to stain for Bcl-2, a survival factor normally expressed by trophoblasts in both the placenta and the uterine wall. Our results show that preeclampsia is associated with widespread apoptosis of cytotrophoblasts that invade the uterus. The magnitude of programmed cell death in this population may account for the sudden onset of symptoms in some patients, as well as the associated coagulopathies.
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PMID:Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. 1039 61

Apoptosis in human placental villi is reported to increase until close to delivery. However, the involvement of the apoptotic process in the initiation of labor, and more particularly in relation to the decrease in placental perfusion during uterine contractions, remains unknown. The purpose of the study was to examine the reactivity of the apoptotic machinery in term placentae obtained before or after the onset of labor and after in vitro incubations. The incidence of apoptotic nuclei (< 1%) as evidenced by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, and the histological distribution of immunoreactive Bcl-2, Bax, and Bcl-x proteins, were similar in placentae collected after delivery and before the onset of labor and in placental explants maintained overnight at 4 degrees C in a minimal salt-Hepes medium. By contrast, 28% of nuclei contained fragmented DNA when placental explants were incubated overnight at 37 degrees C. This marked increase was associated with a decrease in the intensity of the Bcl-2 immunostaining and an increase in the intensity of Bax and Bcl-x immunostaining. In conclusion, the present study clearly evidences the presence of an active apoptotic machinery in term placental cells that is not involved in normal parturition.
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PMID:Apoptosis in human term placenta is not increased during labor but can be massively induced in vitro. 1041 27

There is a type of arteriosclerosis with remodeling of middle-size arteries in which intimal hyperplasia of smooth muscle cells (SMCs) plays the main role, and there are few macrophages, T lymphocytes, and foam cells. It is unknown whether apoptosis and the expression of Bax, an inducer of apoptosis, are increased according to the progression of this type of human arteriosclerosis, which is different from so-called atherosclerosis. Bax heterodimerizes with Bcl-2, an inhibitor of apoptosis, and the ratio of Bax to Bcl-2 determines cellular apoptosis or survival. Thus, we investigated apoptosis and the expressions of Bax, bax mRNA, and Bcl-2 in human arteriovenous (AV) fistulas used for hemodialysis, a representative of arteriosclerosis of the aforementioned type. The material was 20 radial arteries obtained from 20 patients with chronic renal failure undergoing AV shunt surgery. SMCs, macrophages, and T lymphocytes were immunohistochemically identified at the light microscopic (LM) level. Apoptosis was detected by in situ terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end labeling (TUNEL) at both the LM and electron microscopic (EM) level. Cell proliferating activity was estimated by proliferating cell nuclear antigen (PCNA). Bax and Bcl-2 were detected by immunohistochemistry and Western blot analysis. Expression of bax mRNA was detected by in situ hybridization. LM TUNEL-positive cells in both the intima and media were significantly increased according to the percent stenosis of the vessels. EM analysis revealed that ultrastructures of apoptotic SMCs were seen in both synthetic and contractile phenotypes. Their frequency of occurrence in the intima and media were greater in those vessels with >50% stenosis than in those with <50% stenosis (5.2+/-0.7% versus 1.0+/-0.3% in the intima and 2. 1+/-0.5% versus 0.2+/-0.1% in the media). The proportion of apoptotic SMCs with ruptured plasma membranes was greater than that of apoptotic SMCs with intact membranes in the intima of the former (4.1+/-0.6% versus 1.1+/-0.1%). Only those SMCs with apoptotic ultrastructures had TUNEL-positive nuclei with moderate or marked accumulation of immunogold particles at the EM level. However, ultrastructures of oncosis (primary necrosis) were not observed. Immunohistochemical analyses showed significant positive correlations between percent stenosis of vessels and the percentage of either PCNA-positive intimal cells or Bax-positive areas in the intima and media. Bcl-2-positive cells were not observed in the intima but mainly in the outer media. The percentage of Bcl-2-positive medial cells was definitely decreased at an early stage after formation of the AV fistula but did not change according to the duration of hemodialysis or the progression of arteriosclerosis. Western blot analysis of Bax or Bcl-2 and in situ hybridization of bax mRNA confirmed the immunohistochemical data. Thus, regulation of cellularity in intimal hyperplasia of SMCs in human arteriosclerosis with remodeling is mediated by proliferation and apoptosis but not oncosis. The apoptosis is probably induced by an increase in the Bax to Bcl-2 ratio.
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PMID:Apoptosis and overexpression of bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries : analysis with arteriovenous fistulas used for hemodialysis. 1047 47


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