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)

Insulin-like growth factor I (IGF-I) is an important survival growth factor that has been shown to inhibit apoptosis, but the effects of IGF-I on apoptotic signaling remain largely unknown. To investigate IGF-I actions on apoptosis of H9C2 cardiac muscle cells, we have defined the effects of IGF-I on Bcl-2, Bax, caspase 3, DNA fragmentation, and cell survival. The abundance of Bcl-2 and Bax was determined with immunoblotting, and the activities of caspase 3 were assayed with the labeled substrate DEVD-p-nitroanilide. The occurrence of apoptosis was determined by electrophoresis of labeled DNA fragments and by in situ terminal deoxynucleotidyl transferase UTP nick end labeling assay. We found that apoptosis of H9C2 cells, induced by serum withdrawal and doxorubicin, was associated with the induction of Bax and the activation of caspase 3. IGF-I partially inhibited Bax induction, caspase 3 activation, DNA fragmentation, and enhanced cell survival. Interestingly, there is a compensatory rise in the abundance of Bcl-2 upon serum withdrawal and doxorubicin treatment, and IGF-I stimulation resulted in decreased induction of Bcl-2. These results suggest that serum withdrawal- and doxorubicin-induced apoptosis of H9C2 cells probably in part resulted from induction of Bax and caspase 3, and IGF-I inhibited apoptosis by attenuating Bax induction and caspase 3 activation.
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PMID:Insulin-like growth factor I modulates induction of apoptotic signaling in H9C2 cardiac muscle cells. 949 72

Thyrocytes, that generate and use hydrogen peroxide (H2O2) to synthesize thyroid hormones, undergo apoptosis, as do most cell types, when exposed in vitro to H2O2. We have studied 1) the kinetics and the amplitude of the apoptotic response to H2O2 and 2) the relationship between the extent of the apoptosis-inducing effect of H2O2, the H2O2 degradation activity, and the level of expression of apoptosis regulatory proteins, Bcl-2 and Bax, in pig thyrocytes in primary culture. Cells were seeded at high density to obtain confluent monolayers and were cultured in the presence of TSH to maintain the expression of differentiation. H2O2 (10-300 microM) induced the appearance of cells with fragmented DNA (terminal transferase deoxy-UTP-fluorescein isothiocyanate nick end labeling-positive cells) at a maximum of 3-4 h after H2O2 addition and then the detachment of apoptotic cells from the cell monolayer. The proportion of detached cells increased with H2O2 concentration and amounted to up to 30% of the initial cell number after 24 h. The transient effect of H2O2 was related to its rapid degradation by cells and culture medium components (rate constant, approximately 0.1 min(-1)). Iterative additions of H2O2 produced cumulative apoptotic waves. The amplitude of the apoptotic response of thyrocytes to H2O2 progressively increased with the time of culture, up to 4-fold from days 1-8. This was not related to a change in the capacity of thyrocytes to degrade H2O2. During the same period of culture, the Bcl-2 cell content progressively decreased, whereas that of Bax concomitantly increased; thus, the Bcl-2/Bax ratio varied from about 6 on day 1 to 0.5 on day 10. These data show that the susceptibility of thyrocytes to undergo apoptosis increases with the time of culture and that the pronounced changes in the apoptotic status ofthyrocytes might be linked to coordinate modifications of the level of expression of pro- and antiapoptotic regulatory proteins.
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PMID:Susceptibility of differentiated thyrocytes in primary culture to undergo apoptosis after exposure to hydrogen peroxide: relation with the level of expression of apoptosis regulatory proteins, Bcl-2 and Bax. 1021 46

The expression of the pro-apoptotic proteins (Bax, Bak) and anti-apoptotic proteins (Bcl-2, Bcl-X, Mcl-1) was studied by immunohistochemistry in 110 invasive ductal breast carcinomas. The results were correlated with tumour grade, expression of oestrogen receptor (ER) and p53 protein, and the apoptotic index by combined morphology, immunohistochemistry, and a terminal UTP nick end labelling (TUNEL) procedure. Overall, Bcl-2, Bcl-X, Mcl-1, Bax, Bak, ER, and p53 were detected in 62, 75, 68, 75, 60, 68 and 26 per cent of the cases respectively, but at different levels in each case. A high apoptotic index was correlated with high tumour grade (p<0.001), overexpression of p53 (p<0.001), Bak expression (p<0.001), and low expression of Bcl-2 (p<0.001) and ER (p<0.001). No correlation was found between the apoptotic index and Bax, Bcl-X, and Mcl-1 immunostaining results. The expression of Bcl-2 and Bcl-X was correlated to that of ER. Overall, the results of this study strongly suggest that Bcl-2 and Bak expression is critical in regulating apoptosis in breast carcinomas.
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PMID:In vivo patterns of Bcl-2 family protein expression in breast carcinomas in relation to apoptosis. 1039 99

The ability of estrogen to prevent glucocorticoid-induced apoptosis in osteoblasts was studied both in vitro and in vivo. Glucocorticoid treatment for 72 h produced a dose-dependent increase in the number of apoptotic cells, determined by acridine orange/ethidium bromide staining, with a maximal response of 31+/-2% and 26+/-3% with 100 nM corticosterone in primary rat and mouse osteoblasts, respectively. Simultaneous administration of varying concentrations of 17beta-estradiol and 100 nM corticosterone decreased apoptotic osteoblasts in a dose-dependent manner, with a maximal decrease of 70% with 0.01 nM 17beta-estradiol. Terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling also demonstrated glucocorticoid-induced DNA fragmentation that was inhibited by estrogen. Estrogen was shown to inhibit apoptosis induced by lipopolysaccharide treatment. As early as 6 h, Western blots demonstrated a dose-dependent decrease in the Bcl-2/Bax ratio, which reached a minimum of 0.18 in osteoblasts treated with 1000 nM corticosterone for 72 h. This reduction in Bcl-2/Bax was abolished by treating osteoblasts simultaneously with 17beta-estradiol, but not with 17alpha-estradiol. In 7-day-old mice, administration of varying concentrations of dexamethasone for 72 h resulted in a dose-dependent increase in the number of apoptotic osteoblasts as demonstrated by in situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling staining of calvaria. A maximum of 22+/-1% apoptotic osteoblasts on the bone surface was found with 1 mg/kg BW dexamethasone compared with 2+/-1% in vehicle-treated mice. Injection of varying concentrations of 17beta-estradiol (0.5-5 mg/kg BW), but not 17alpha-estradiol, with 1 mg/kg dexamethasone produced a dose-dependent decrease in the number of apoptotic osteoblasts to 5+/-1% with 5 mg/kg 17beta-estradiol. Thus, glucocorticoid-induced apoptosis of osteoblasts may be prevented at least in part by 17beta-estradiol.
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PMID:Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. 1053 65

This study aimed to examine the temporal profile of neuronal apoptosis in the central nervous system (CNS) following closed head injury in rat. Fos immunoreactivity was detected in neuronal nuclei in the cerebral cortex at 2 h after head injury. At 4 h, Bax protein expression was elevated with a concomitant down-regulation of Bcl-2 expression. Along with this, a marked immunoexpression of p53 was also observed in these cells. Double immunolabelling study has shown the colocalization of Bax immunoreactivity with Bcl-2 and p53. In rats killed 1 day after injury, a variable number of transferase d-UTP nick-end labelling positive cells were observed. Present findings suggest that the upregulation of p53 and a shift in the ratio of Bcl-2 to Bax may contribute to neuronal apoptosis in the CNS after closed head injury.
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PMID:Changes in apoptosis-related protein (p53, Bax, Bcl-2 and Fos) expression with DNA fragmentation in the central nervous system in rats after closed head injury. 1093 84

The mitochondrial toxin 3-nitropropionic acid (3-NP) causes selective striatal lesions in rats and serves as an experimental model for the neurodegenerative disorder Huntington's disease (HD). Apoptotic cell death has been implicated for the neuronal degeneration that occurs in HD brains. The present study was designed to investigate whether the 3-NP-induced cell death in rats involves apoptosis and an altered expression of Bcl-2 family proteins. Systemic administration of 3-NP via subcutaneous Alzet pumps resulted in lesions of variable severity with neuronal loss and gliosis in the striatum. Using the terminal transferase-mediated biotinylated-UTP nick end-labelling (TUNEL) of DNA, TUNEL-positive cells exhibiting typical apoptotic morphology were detected only in the striatum of rats with a severe lesion. Furthermore, the neuronal expression of the pro-apoptotic protein Bax was strongly increased in the core of the severe lesion. Expression of the anti-apoptotic marker Bcl-2 was unchanged in this location, but was enhanced in the margins of the lesions. A moderately increased expression of both Bax and Bcl-2 was observed in dark neurones in the mild lesion and in the subtle lesion. The presence of nuclear DNA fragmentation, strong granular Bax expression and an increased Bax/Bcl-2 ratio in the centre of severe lesions suggests the occurrence of apoptotic cell death following 3-NP administration. In contrast, the dark compromised neurones observed in 3-NP-treated animals revealed an equally enhanced expression of both Bax and Bcl-2, but lacked TUNEL-labelling, and are therefore not apoptotic.
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PMID:The mitochondrial toxin 3-nitropropionic acid induces differential expression patterns of apoptosis-related markers in rat striatum. 1129 4

The aim of the preliminary study was to evaluate the role of apoptosis and proliferation of myocytes in order to predict the prognosis and optimal treatment of patients with end-stage dilated cardiomyopathy. Endomyocardial biopsy was performed during open-heart surgery (reductive annuloplasty of double orifice) in 19 patients with end-stage dilated cardiomyopathy. The terminal deoxynucleotidyl transferase d-UTP-biotin nick-end labelling (TUNEL) method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis such as proto-oncogene Bcl-2 (B-cell lymphoma gene), and proliferative markers such as proliferation cell nuclear antigen (PCNA) and Ki-67 proliferative antigen. The increased percentage of apoptotic myocytes and decreased expression of bcl-2 is associated with earlier death after surgery. Increased expression of proliferation markers of myocytes in patients who survived seven years after surgery compared to those who died within three years suggest that adult cardiomyocytes are not terminally differentiated and this might represent potential growth reserve of the diseased heart. Based on our preliminary study we may conclude that myocytes' apoptosis and proliferative activity might help us to predict the prognosis and optimal treatment of patients with end-stage dilated cardiomyopathy.
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PMID:Myocytes' apoptosis and proliferation in endomyocardial biopsy as prognostic factors in terminal heart failure. 1167 24

Exposure of organotypic rat corticostriatal slice cultures to the mitochondrial toxin 3-nitropropionic acid (3-NP) resulted in concentration-dependent loss of cresylviolet-stained cells and increase of lactate dehydrogenase and lactate efflux into the culture medium, indicators for cell death and metabolic activity in the slices, respectively. The involvement of apoptosis in these slices was suggested by using the terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL) technique, and immunohistochemistry for the apoptosis-related markers Bax and Bcl-2. In 3-NP-exposed slices, TUNEL-positive cells were observed in both the striatum and the cortex but in different forms: striatal neurons were either diffusely stained or showed nuclear fragmentation, cortical neurons only exhibiting nuclear fragmentation. In 3-NP-exposed slices, the pro-apoptotic protein Bax was abundantly expressed, whereas the anti-apoptotic protein Bcl-2 was not expressed in striatal neurons. We suggest that both apoptosis and necrosis are involved in the 3-NP-treated slices, apoptosis as well as necrosis in the striatum and apoptosis in the cortex.
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PMID:3-Nitropropionic acid induces cell death and mitochondrial dysfunction in rat corticostriatal slice cultures. 1216 Dec 69

Apoptosis occurs in the growth plate during normal and abnormal longitudinal growth. To investigate the role of apoptosis during growth plate maturation, apoptosis and apoptosis-related proteins were studied in rat tibial growth plates at 2, 4, 8, and 11 wk of age. Apoptosis was studied by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-UTP nick end-labeling (TUNEL) method, and immunohistochemistry was used to detect p53, caspase-3 and -6, the antiapoptotic proteins Bcl-2 and Bcl-x, and the proapoptotic proteins Bax and Bad. In all age groups studied, most apoptotic chondrocytes were terminal hypertrophic chondrocytes (THPCs) with a significant increase during development. At 2 wk, 0.108 +/- 0.026 THPCs were found to be apoptotic per millimeter of growth plate width; at 4 wk, 0.355 +/- 0.048; at 8 wk, 0.394 +/- 0.043; and at 11 wk, 1.084 +/- 0.069 (p < 0.001; 11 wk vs 2, 4, and 8 wk). THPCs were negative for p53 immunoreactivity at 2 and 4 wk, whereas some THPCs were positive at 8 and 11 wk. Caspase-3 and -6 were found in proliferative and early hypertrophic cells at 2 wk, whereas mature hypertrophic cells and THPCs were negative. At later stages of development, mature hypertrophic cells and THPCs were stained for both caspase-3 and -6. Bcl-2 and Bcl-x were present in proliferative and early hypertrophic cells at 2 wk, whereas at older ages a decrease in staining was observed. At 2 wk of age, Bax and Bad immunoreactivities were localized in proliferative and early hypertrophic cells, whereas at 8 and 11 wk many mature hypertrophic cells and THPCs were immunoreactive for Bax and Bad. Our results show that apoptosis is developmentally regulated in the rat growth plate. In older animals, with decreased growth rate and growth plate height, apoptosis is significantly increased, especially in THPCs.
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PMID:Apoptosis is developmentally regulated in rat growth plate. 1245 Mar 19

Distribution of apoptotic cells and expression of the apoptosis-related factors p53, bcl-2 and bad during morphogenesis of the murine palatine rugae (PR) were examined histochemically using the terminal deoxynucleotidyl transferase-mediated UTP nick end-labeling (TUNEL) technique and specific antibodies against apoptosis and cell cycle-related molecules. Formation of the PR rudiment was controlled by cell proliferation and apoptosis in the palatal epithelium. TUNEL-positive cells were detected only at the epithelial placode area at 12.5-13.5 days post coitus (dpc), but only a few cells were positive at the protruding PR area at 14.5-16.5 dpc. Bcl-2 protein was expressed mainly in the areas outside of those containing TUNEL-positive cells at 15.5 -6.5 dpc. P53 protein was not detected throughout gestation. Bad was detected in the epithelial layer at 13.5 and 15.5 dpc and overlapping the apoptotic area at 13.5-15.5 dpc. Apoptosis of palatal epithelial cells might therefore involve spatiotemporally regulated expression of bad during murine PR development.
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PMID:Distribution of apoptotic cells and apoptosis-related molecules in the developing murine palatine rugae. 1252 Jan 1


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