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)

The induction of apoptosis by contrast media (CM) and mannitol (M) was investigated in the hearts and kidneys of 12-mo-old male SHR rats. Ten groups of 3 SHR rats received a dose of 5 ml/kg of one of the following: Hypaque (H)-30, H-60, H-76, Omnipaque (O)-140, O-350, mannitol (M)-4%, M-9%, M-19%, M-27%, or saline (S). DNA fragmentation was detected using the terminal deoxynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL) method, and the morphology characteristics of apoptosis were confirmed in cardiac and renal cells. The immunoreactivities of Bcl-2, Bax, and p53 were assessed immunohistochemically in the kidneys. Apoptosis occurred in cardiac myocytes and renal tubular and glomerular cells as well as in vascular endothelial and smooth muscle cells of the heart and kidneys. The high frequency of apoptosis correlated significantly with the increase in the osmolality of the H, O, and M. The increased Bax, the increased p53, and the decreased Bcl-2 immunoreactivities were detected in H- or O-treated, but not in M-treated, rats. These findings suggest that CM and M activate cardiac and renal apoptosis by different mechanisms and that the apoptotic process may be implicated in acute heart and renal damage.
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PMID:Contrast medium- and mannitol-induced apoptosis in heart and kidney of SHR rats. 1048 23

The outcome of myocardial ischemia-reperfusion has been partially attributed to the degree of apoptosis in cardiomyocytes. Aggregating platelets by release of transforming growth factor-beta(1) (TGF-beta(1)) protect the isolated heart against ischemia-reperfusion injury and preserve myocardial TGF-beta(1) content. To gain more insight into the modulation of hypoxia-reoxygenation-induced injury (apoptosis and necrosis) to myocytes by TGF-beta(1) and aggregating platelets, cultured adult rat myocytes were exposed for 48 or 72 h to hypoxia alone, or to hypoxia followed by 3 h of reoxygenation. Apoptosis in the cells was determined by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining and DNA fragmentation on gel electrophoresis. Hypoxia alone caused a time-dependent increase in myocyte apoptosis (number of apoptotic cells: 19+/-3% at 48 h and 39+/-5% at 72 h compared with 5+/-1% in control cells, based on a 500-cell count). Three hours of reoxygenation after 48 h of hypoxia further increased the number of apoptotic cells (34+/-8 versus 19+/-3% in hypoxia for 48 h), but reoxygenation after 72 h of hypoxia did not additionally increase the number of apoptotic cells, perhaps because of extensive cell necrosis on prolonged hypoxia. Forty-eight hours of hypoxia followed by 3 h of reoxygenation also resulted in a decrease in Bcl-2 and an increase in Fas protein level. Incubation of myocytes with either recombinant TGF-beta(1) (0.5-5 ng/ml) or aggregated platelet supernatant (from 2-3 x10(7) platelets/ml, containing approximately 0.5 ng/ml of TGF-beta(1)) markedly (P<.01) decreased the number of apoptotic cells after hypoxia-reoxygenation. Incubation with TGF-beta(1) also reduced myocyte necrosis as evident from lactate dehydrogenase release and trypan blue dye exclusion. These data demonstrate that hypoxia-reoxygenation results in apoptosis and necrosis in cultured adult rat myocytes; this can be attenuated by TGF-beta(1). Similarity of data with TGF-beta(1) and aggregated platelet supernatant suggests that platelet-mediated cardioprotection during hypoxia-reoxygenation may relate in part to the release of TGF-beta(1).
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PMID:Hypoxia-reoxygenation-induced apoptosis in cultured adult rat myocytes and the protective effect of platelets and transforming growth factor-beta(1). 1052 94

Apoptotic bodies are frequently found in oligodendrogliomas, particularly in the anaplastic subtype. A range of proteins, such as those of the Bcl family, are implicated in the control of apoptosis. The ratio of antagonists of apoptosis, such as Bcl-2, to agonists, such as Bax, is thought to determine the outcome for a particular cell. This study aimed to determine the expression of Bcl-2 and Bax proteins in a series of oligodendrogliomas and to relate the expression of these to measures of apoptosis. Immunohistochemistry was used to detect the expression of Bcl-2 and Bax in an archival series of 32 oligodendrogliomas. The results were scored semiquantitatively for the extent and intensity of tumour staining. Apoptosis indices were determined by counting apoptotic bodies on haematoxylin and eosin staining and the percentage of cells showing a positive reaction with the TdT-mediated dUTP-biotin nick end-labelling technique (TUNEL). Granular cytoplasmic staining for Bcl-2 was seen in tumour cells in 81% of cases. Cases with a strong intensity (but not extent) of staining showed a lower TUNEL index (P=0.038). Bcl-2 expression was identified in the walls of intratumoural blood vessels in 55% of cases and in peri-tumoural neurones (where present) in 87%. Bax expression was detected in tumour cells in 69% of cases but no relationship to TI was detected. Bax positivity was seen in blood vessels in 44% of cases and peri-tumoural neurones in 60%. Bcl-2 and Bax were concluded to be expressed in a high proportion of oligodendrogliomas, suggesting that they may exert a regulatory role in cell death in these tumours.
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PMID:Expression of Bcl-2 and Bax in oligodendrogliomas and their relationship to apoptosis. 1056 30

We previously showed that soluble, pepsin-solubilized collagen VI increases de novo DNA synthesis in serum-starved HT1080 and 3T3 fibroblasts up to 100-fold compared with soluble collagen I, reaching 80% of the stimulation caused by 10% fetal calf serum. Here we show that collagen VI also inhibits apoptotic cell death in serum-starved cells as evidenced by morphological criteria, DNA laddering, complementary apoptosis assays (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorting), and quantification of apoptosis-regulating proteins. In the presence of starving medium alone or collagen I, the proapoptotic Bax was up-regulated 2-2.5-fold, compared with soluble collagen VI and fetal calf serum, whereas levels of the antiapoptotic Bcl-2 protein remained unaffected. In accordance with its potent stimulation of DNA synthesis, soluble collagen VI carries serum-starved HT1080 and Balb 3T3 fibroblasts through G(2) as shown by fluorescence-activated cell sorting analysis, whereas cells exposed to medium and collagen I where arrested at G(1)-S. This was accompanied by a 2-3-fold increase in cyclin A, B, and D1 protein expression. Collagen VI-induced inhibition of apoptotic cell death may be operative during embryogenesis, wound healing, and fibrosis when elevated tissue and blood levels of collagen VI are observed, thus initiating a feedback loop of mesenchymal cell activation and proliferation.
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PMID:Soluble collagen VI drives serum-starved fibroblasts through S phase and prevents apoptosis via down-regulation of Bax. 1056 13

The aim of this study was to examine the relationship between apoptosis, protein expression of apoptosis mediator and inhibitor genes p53 and bcl-2 and various histopathological grades of squamous cell carcinoma of the esophagus. Apoptotic index was evaluated in thirty human esophageal squamous cell carcinomas and adjoining normal tissue by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL). Protein expression of bcl-2 and p53 was measured by immunohistochemical staining of cryocut sections and Western blotting. Apoptototic cells were seen mainly around areas of keratinization and the apoptotic index was highest in well-differentiated squamous cell carcinomas. High Bcl-2 expression correlated inversely with the apoptotic index. p53 protein expression did not correlate with the grade of the tumor or the apoptotic index. We propose that deregulation of apoptosis contributes to the pathogenesis of esophageal squamous cell carcinoma.
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PMID:Bcl-2 expression is correlated with low apoptotic index and associated with histopathological grading in esophageal squamous cell carcinomas. 1060 36

Apoptosis is associated with acute rejection, transplant vascular disease, and the "Quilty effect" in cardiac allografts. However, the causality and mechanisms of apoptosis in the pathogenesis of vascular injury are poorly understood. In the current study, the Lewis-to-F344 rat cardiac allograft model was utilized as a means to immunohistochemically evaluate the expression of Bax, Bcl-2, and factor VIII-related antigen in transplant vascular disease. Apoptosis was detected by in situ labeling of fragmented DNA using in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in native hearts and grafted hearts of allogeneic and syngeneic recipients. Bax immunostaining was detected in 50% of endothelial cells, in 60% of infiltrating leukocytes associated with acute rejection in the myocardium, and in certain other parenchymal cells, considering all cardiac allografts. More than 75% of infiltrating leukocytes in the intima of vessel walls immunostained positive for Bax. Bcl-2 immunopositivity was not detected in native hearts, allo allo-, or syngrafts. On Days 2, 4, 7, and 14 after transplantation, TUNEL positivity was detected in only about 1% of leukocytes in the interstitial infiltrates, despite the fact that rather severe rejection was observed in Day 14 allografts. The number of apoptotic leukocytes increased significantly by Days 28 and 56 after transplantation, although the severity of histopathological rejection did not increase as compared with Day 14. The apoptotic leukocytes remained isolated or in small clusters, mainly perivascular. TUNEL positivity colocalized with Bax expression in these cells. TUNEL staining was also observed in certain parenchymal cells in the interstitium and in randomly distributed inflammatory cells in vessel walls. TUNEL positivity was detected in rare luminal endothelial cells in transverse sections of vessel walls (about 10% of cells in <1/10 of the vessels studied). Nuclear TUNEL positivity was observed in Bax-negative cardiomyocytes in ischemically damaged areas of myocardium in both allografts and syngrafts. In summary, increased expression of Bax was observed in rat cardiac allografts. The colocalization of TUNEL and Bax suggests that endothelial cell injury and infiltrating leukocyte apoptosis may be regulated in part by the apoptosis-promoting protein, Bax. In the current model, myocyte death due to ischemia and surgical injury in syngrafts and allografts does not seem to involve Bax.
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PMID:Bax and apoptosis in acute and chronic rejection of rat cardiac allografts. 1061 13

Glutamate has been shown to function as a toxic agent in neuronal and glial cells, as well as an excitatory neurotransmitter throughout the central nervous system. In the present study, we examined the effect of increasing glutamate concentration on the induction of apoptosis in the two human glioblastoma cell lines GB-4 and GB-12. Glutamate exposure caused cell death of GB-4 and GB-12 in a dose-dependent manner. The cells were found to die via apoptosis in response to glutamate based on the following criteria: propidium iodide (PI) staining, H-E staining, electron microscopic analysis, and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The glutamate-induced apoptosis appears to involve the modulation of Bcl-2 family gene products such as Bcl-2, Bcl-xL, and Bax-alpha. Both Bcl-2 and Bcl-xL were down-regulated by glutamate at 24 h and further at 48 h. The apoptosis-promoting product p21 Bax-alpha was also down-regulated in GB-12 but slightly up-regulated in GB-4, accompanied by generation of variant form of p18 Bax-alpha in both cell lines. These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism which appears to involve the Bcl-2/Bax-alpha molecular complex.
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PMID:Participation of Bcl-2/Bax-alpha in glutamate-induced apoptosis of human glioblastoma cells. 1061 94

Bcl-2 and p53 gene products have been both linked to cell death by apoptosis. In the present study, we examined the relationship of Bcl-2 and p53 protein expression, p53 mutation and apoptosis in normal human ovaries and different types of human ovarian epithelial tumors by immunohistochemical localization, in situ terminal transferase-mediated dUTP nick end labeling and polymerase chain reaction-single strand conformation polymorphism. It was found that Bcl-2 expressed strongly in the surface epithelium of normal ovaries and benign and borderline ovarian tumors but weakly in the malignant tumors. On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium. A significant inverse correlation between Bcl-2 and p53 expression was found in the malignant ovarian tumors examined. p53 gene mutation at exons 5-11 was however not a pre-requisite for p53 expression in both borderline and malignant tumors. Apoptotic activities, as reflected by apoptotic indices, were low in normal ovarian surface epithelium and benign tumors but were increased in borderline and malignant tumors, with the highest average apoptotic index found in grade III malignant tumors. Statistical analyses showed a positive correlation between apoptosis and p53 expression, but similar correlation was not found between apoptosis and Bcl-2 expression. Our results also indicate that although expression of Bcl-2 is important during ovarian carcinogenesis, the Bcl-2 protein may have other roles to play apart from being a modulator of apoptosis in human ovarian epithelial cancers.
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PMID:Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers. 1066 69

Pre-eclampsia is a serious pregnancy complication diagnosed by signs of widespread maternal endothelial dysfunction. In normal pregnancy, a subpopulation of placental cytotrophoblast stem cells executes a differentiation programme 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. In pre-eclampsia, cytotrophoblasts fail to differentiate along the invasive pathway. The functional consequences of this abnormality negatively affect interstitial and endovascular invasion, thereby compromising blood flow to the maternal-fetal interface. To determine whether abnormal differentiation and/or hypoxia leads to apoptosis of invasive cytotrophoblasts, we used the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) 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 little or no apoptosis in any location, but in samples from patients with pre-eclampsia, 15-50% of the cytotrophoblast subpopulation that invaded the uterine wall was labelled (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 pre-eclampsia 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:Invasive cytotrophoblast apoptosis in pre-eclampsia. 1069 Aug 1

Overexpression of wild-type p53 in cancer cells by adenovirus-mediated p53 gene transfer can result in the induction of apoptosis. To identify the potential mediators of this p53-induced apoptosis, we examined apoptotic protein levels in human lung cancer cells after Adp53 gene transfer. We observed up-regulation of Bax and Bak protein levels 18-36 h after transduction with Adp53 in H1299, H358, and H322 lung cancer cells. Contrary to expected observations, no changes in Bcl-2 and Bcl-X(L) protein levels were observed. Morphological cell changes and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining showed evidence of apoptosis in all cell lines 48 h after transduction with Adp53. These results indicate that the induction of apoptosis by adenovirus-mediated p53 transfer may be mediated by the induction of proapoptotic mechanisms rather than suppression of antiapoptotic mechanisms.
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PMID:Up-regulation of the proapoptotic mediators Bax and Bak after adenovirus-mediated p53 gene transfer in lung cancer cells. 1074 12


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