Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoid hormones are known to enhance gonadotropin/cAMP-induced steroidogenesis in rat and human granulosa cells. As glucocorticoids induce apoptosis in numerous cell types, we investigated the role of glucocorticoids in the control of apoptosis in immortalized human granulosa cells (HO-23) transfected with a temperature-sensitive mutant of p53 (Val(135)). When HO-23 were incubated with forskolin in the presence or absence of dexamethasone (Dex) at 32 or 37 C, progesterone production was higher by 4- and 8-fold in the presence of Dex at 37 or 32 C, respectively (P: < 0. 01). The expression of adrenodoxin (ADX), which is an intrinsic part of the cytochrome P450 side-chain cleavage enzyme system, remained the same in the presence or absence of Dex in forskolin-stimulated cells. Dex reduced apoptosis (to 33% of control) in cultures after activation of p53 by shifting the temperature from 37 to 32 C. Moreover, Dex suppressed apoptosis induced by serum deprivation (to 40% of control) or forskolin stimulation (to 28% and 40% at 37 and at 32 C, respectively). The protective effect of Dex on cAMP-, p53-, and serum deprivation-induced apoptosis was confirmed by both 4',6-diamido-2-phenylindole hydrochloride DNA staining and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling with an ED(50) of 7 nM Dex. Hydrocortisone showed a similar antiapoptotic effect. The protective effect of glucocorticoids against apoptosis was completely abolished by RU486 when cells were coincubated with 10 nM Dex and 10-100 nM RU486. The protection against apoptosis by glucocorticoid involved a sharp elevation in intracellular levels of Bcl-2 (3-7.6 fold; P: < 0.01). In contrast to the effect of Dex in the prevention of apoptosis in HO-23 granulosa cells, Dex dramatically stimulated apoptosis by 3-fold in LTR-6 myeloid leukemia cells expressing the same temperature-sensitive mutant (Val(135) p53) and the same amount of glucocorticoid receptor-alpha. Forskolin did not stimulate apoptosis when incubated with these cells. However, it augmented by 1.2-fold the p53-induced apoptosis in cells shifted from 37 to 32 C. Dex further enhanced apoptosis by 1.9-fold in p53-activated cultures (32 C). Incubation of the cells with Dex dramatically reduced Bcl-2 levels to 15% of control at 37 C (P: < 0.01) or 32 C in the presence or absence of forskolin (P: < 0.01). Our data suggest that glucocorticoids exert a protective effect against induced apoptosis in immortalized granulosa cells and a stimulatory effect on apoptosis in myeloid leukemia cells. Moreover, modulation of Bcl-2 levels plays an important role in mediating the glucocorticoid effect on cell survival. The opposite effect of glucocorticoids on Bcl-2 levels in the two cell lines may be due to the different ontogeneses of the two cell types: epithelial for granulosa cells vs. mesenchymal for myeloid cells studied in the present work.
 ...
PMID:Glucocorticoids protect against apoptosis induced by serum deprivation, cyclic adenosine 3',5'-monophosphate and p53 activation in immortalized human granulosa cells: involvement of Bcl-2. 1115 53

Recent studies have suggested that apoptosis is one of the pathogenetic mechanisms in rheumatoid arthritis (RA). In this study, by using single and double immunohistochemical staining assays, Fas, Fas-L, p53, and Bcl-2 were measured simultaneously in RA and osteoarthritic (OA) and post-traumatic (PT) synovial tissues (ST) in order to understand the distribution of these apoptosis-related proteins. The TdT-mediated dUTP-biotin nick end labelling (TUNEL) method was performed to detect apoptotic cells. There was a significant increase of Fas, Fas-L, and p53 in RA ST, compared with OA or PT, but no significant difference of Bcl-2 expression was detected between patient groups. In RA ST, expression of Fas and p53 was detected in sub-lining layers and the majority of Fas- and p53-expressing cells were fibroblast-like synoviocytes. A positive correlation between Fas and p53 was demonstrated in RA ST. In RA ST, one-third of Fas-positive and 80% of p53-positive cells were also TUNEL-positive. These results indicate that apoptosis in RA is strongly associated with the expression of Fas and p53, but not Bcl-2.
 ...
PMID:Apoptosis in rheumatoid arthritis--expression of Fas, Fas-L, p53, and Bcl-2 in rheumatoid synovial tissues. 1116 23

The role of endogenous NO on cell survival was investigated in human melanoma cells and melanocytes. Inducible NO synthase (iNOS) was always expressed in a panel of melanoma cell lines from metastatic lesions and in normal adult melanocytes. iNOS was also detected by immunohistochemistry in melanoma cells from metastases. Release of NO by tumor cells and melanocytes was inhibited by a specific iNOS inhibitor, aminoguanidine (AMG). Inhibition of endogenous NO synthesis did not affect cell cycle progression of melanoma cells but led to cell death by apoptosis, as indicated by Annexin V/propidium iodide and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assays. By contrast, iNOS inhibition by AMG did not promote apoptosis in normal adult melanocytes. A mitochondrial pathway was involved in melanoma apop tosis, as indicated by altered mitochondrial membrane potential (delta psi(m)) and down-regulation of Bcl-2 protein level after iNOS inhibition. AMG treatment triggered release of caspase-1, enzymatic activation of caspase-3, and degradation of poly(ADP-ribose) polymerase, one of the main caspase-3 substrates. Melanoma cell apoptosis induced by iNOS inhibition was completely blocked by peptide inhibitors of caspase-1 and caspase-3 (Ac-DEVD-CHO and AC-YVAD-CHO) or by an exogenous NO donor, sodium nitroprusside, or by addition of serum. Finally, comparison of control and AMG-treated melanoma cells by pathway-specific gene array analysis indicated that inhibition of NO synthesis led, before induction of apoptosis, to up-regulation of mRNA levels of genes involved in the apoptosis pathway such as Bax, caspase-1, caspase-3, caspase-6, gadd45beta, mdm2, and TRAIL. Taken together, these results indicate that melanoma cell survival is regulated by endogenous NO resulting from iNOS activity.
 ...
PMID:Antiapoptotic role of endogenous nitric oxide in human melanoma cells. 1119 80

In previous studies, we showed that basic fibroblast growth factor (bFGF) reduced infarct volume when infused intravenously in animal models of focal cerebral ischemia. In the current study, we examined the potential mechanism of infarct reduction by bFGF, especially effects on apoptosis within the ischemic brain. We found that bFGF decreased DNA fragmentation in the ischemic hemisphere, as assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) histochemical methods combined with morphological criteria. bFGF also prevented reduction of immunoreactivity of the anti-apoptotic protein Bcl-2 in the ischemic hemisphere, but did not alter immunoreactivity of the pro-apoptotic proteins Bax, Caspase-1, or Caspase-3. These changes in TUNEL histochemistry and Bcl-2 immunoreactivity were especially prominent in cortex at the borders ('penumbra') of infarcts, spared by bFGF treatment. We conclude that the infarct-reducing effects of bFGF may be due, in part, to prevention of downregulation of Bcl-2 expression and decreased apoptosis in the ischemic brain.
 ...
PMID:Intravenous basic fibroblast growth factor (bFGF) decreases DNA fragmentation and prevents downregulation of Bcl-2 expression in the ischemic brain following middle cerebral artery occlusion in rats. 1122 61

The mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene (DMBA) in 50-day-old female Sprague--Dawley rats were investigated. A single dose of DMBA, either fed (30 mg) per os or injected (6 mg) in a caudal vein, caused inner cortical cell death (cells of the zonae fasciculata and reticularis) by an apoptotic mechanism. Apoptotic cells were identified by cell morphology, and terminal dUTP nick end labeling (TUNEL)-positive cells were seen at 12 hrs post-DMBA, reached a maximum at 36 h, and were accompanied by blood congestion followed by massive hemorrhage leading to post-apoptotic necrosis at 48 and 72 h. The apoptotic cascade involved the up-regulation of Bax, the down-regulation of Bcl-2, and the activation of caspase-3. At 72 h, regeneration as evidenced by the appearance of 5-bromo-2'-deoxyuridine-positive cells began to occur in the damaged inner cortical zones, with the cells proliferating toward the medulla thereafter. Regenerative cells expressed cytochrome P450 11 beta hydroxylase. The damage was repaired but calcification appeared at 2 weeks post-DMBA, leaving bow-shaped lesions in some adrenals.
 ...
PMID:Mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene in female Sprague--Dawley rats. 1126 59

Twenty-seven cases of primary extranodal oral B-cell lymphoma and 22 cases of primary maxillofacial nodal B-cell lymphoma were investigated for the presence of apoptotic cells and the expression of apoptosis-related gene products by terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry. The majority of extranodal oral diffuse large B-cell lymphomas (17/25, 68%) and maxillofacial nodal diffuse large B-cell lymphomas (14/16, 88%) contained no or less than 10% apoptotic cells. Whereas the majority of extranodal oral diffuse large B-cell lymphomas (18/25, 72%) and maxillofacial nodal diffuse large B-cell lymphomas (13/16, 81%) contained more than 10% of Ki-67-positive cells. Bcl-2-, Bax-, p53- and Ki-67-positive rates were higher in maxillofacial nodal diffuse large B-cell lymphomas than in extranodal oral diffuse large B-cell lymphomas, but only Bax (chi2 test, 0.01<P<0.025) and p53 (chi2 test, 0.005<P<0.01) had significant differences. Extranodal oral diffuse large B-cell lymphomas had a higher frequency of TUNEL expression than maxillofacial nodal diffuse large B-cell lymphomas. In maxillofacial nodal diffuse large B-cell lymphomas, stage III and stage IV tumors had a significantly higher frequency of Bcl-2 expression than stage I and stage II tumors (Fisher's exact test, P<0.01). These findings indicated that in the majority of both extranodal oral and maxillofacial nodal diffuse large B-cell lymphomas, apoptosis was inhibited - whereas proliferative activity was accelerated. Impairment of apoptosis and apoptotic related gene products may have a more important relation to maxillofacial nodal diffuse large B-cell lymphoma than extranodal oral diffuse large B-cell lymphoma.
 ...
PMID:Comparison of apoptosis and apoptosis-related gene products between extranodal oral B-cell lymphoma and maxillofacial nodal B-cell lymphoma. 1127 28

Photodynamic therapy (PDT), a promising treatment modality, is an oxidative stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its therapeutic efficacy. Although studies suggest the involvement of multiple pathways, the triggering event(s) responsible for PDT-mediated apoptotic response is(are) not clear. To investigate the role of Bcl-2 in PDT-mediated apoptosis, we employed Bcl-2-antisense and -overexpression approaches in two cell types differing in their responses toward PDT apoptosis. In the first approach, we treated radiation-induced fibrosarcoma (RIF 1) cells, which are resistant to silicon phthalocyanine (Pc 4)-PDT apoptosis, with Bcl-2-antisense oligonucleotide. This treatment resulted in sensitization of RIF 1 cells to PDT-mediated apoptosis as demonstrated by i) cleavage of poly(ADP-ribose) polymerase, ii) DNA ladder formation, iii) terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and iv) DEVDase activity. This treatment also resulted in oligonucleotide concentration-dependent decrease in cell viability and down-regulation of Bcl-2 protein with a concomitant increase in apoptosis. However, the level of Bax, a pro-apoptotic member of Bcl-2 family, remained unaltered. In the second approach, an overexpression of Bcl-2 in PDT apoptosis-sensitive human epidermoid carcinoma (A431) cells resulted in enhanced apoptosis and up-regulation of Bax following PDT. In both the approaches, the increased Bax/Bcl-2 ratio was associated with an increased apoptotic response of PDT. Our data also demonstrated that PDT results in modulation of other Bcl-2 family members in a way that the overall ratio of pro-apoptotic and anti-apoptotic member proteins favors apoptosis.
 ...
PMID:Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis. 1127 20

We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.
 ...
PMID:Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis. 1133 61

Frontotemporal dementia (FTD) is a neurodegenerative disease associated with aging for which the etiology is unclear. Relatively little is known about the pathology of this disease, which has only recently been a topic of investigation for dementia researchers. Though the known pathology of FTD includes neuron loss, the mechanism of neuronal death is not known. In this study, the authors investigated apoptotic pathways as a possible mechanism of neuronal cell death in FTD. They evaluated immunoreactivity for Bcl-2 family protein members Bcl-x and Bax in postmortem frontal cortex from FTD, AD, and control cases. Bcl-x(L), Bcl-x(S), and Bax all exhibited altered immunoreactivity in FTD cases as compared with control cases. Bcl-x immunoreactivity varied widely among both controls and FTD cases. However, Bcl-x(L) showed strong white matter immunoreactivity in all FTD cases, whereas white matter immunoreactivity was absent in controls. These trends in Bcl-x immunoreactivity suggest a strong white matter involvement in the pathology of FTD. Bax immunoreactivity also varied across all cases. Bax immunoreactivity was observed in terminal transferase dUTP nick ending labeling (TUNEL) positive neurons in both FTD and AD cases. However, one notable finding was immunoreactivity to Bax in astrocytes of FTD cases, as well as endothelial cells of the cerebrovasculature. Neither astrocytic nor endothelial cell immunoreactivity to Bax was exhibited in control or AD cases. Because Bax is a pro-apoptotic protein, this finding suggests the presence of a cerebrovascular component in the pathology of FTD. These findings, coupled with the proposed functions of the Bcl-2 family proteins, suggest that an apoptotic pathway may be responsible for neuron, and possibly astrocyte, death in FTD.
 ...
PMID:Bcl-2 family protein behavior in frontotemporal dementia implies vascular involvement. 1140 49

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.
 ...
PMID:Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts. 1142 Jan 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>