Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that mesothelioma expresses the antiapoptotic protein BCL-XL, but not BCL-2, rendering bcl-xl gene expression a potential therapeutic target. Sodium butyrate (NaB) is a histone deacetylase inhibitor capable of alteration of bcl-2 family protein expression in other tumor types. Mesothelioma cell lines (REN, I-45) were exposed to NaB, and viability (colorimetric assay) and apoptosis (TUNEL, Hoescht staining, flow cytometry) were evaluated. Effects on bcl-2 family protein, fas-fas ligand, and caspases were examined by Western blot analysis and functional assay. An RNase assay evaluated bcl-2 family messenger RNA (mRNA) expression. Overexpressing BCL-XL mesothelioma clones were created by plasmid transfer. Cells were sensitive to NaB at low IC(50) (REN, 0.3 mM; I-45, 1 mM) and demonstrated apoptosis (percentage of cells below G1 phase by flow cytometry [sub-G1]: REN, 38.5%; I-45, 30.9%). A significant decrease in BCL-XL protein expression was noted with BAK, BAX, and BCL-2 unchanged, and this was corroborated at the transcriptional level with selectively decreased bcl-xl mRNA production after sodium butyrate exposure. Fas expression and fas-fas ligand sensitivity were unchanged. Caspases demonstrated low-level activation. Stable overexpressing BCL-XL clones were proportionally resistant to the NaB effect. This study suggests that mesothelioma cells are sensitive to the induction of apoptosis related to the attenuation of antiapoptotic bcl-xl gene and protein expression. Additional study of the therapeutic benefit of targeting bcl-xl gene expression in mesothelioma is warranted.
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PMID:Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. 1171 97

In order to investigate the effects of rhGM-CSF on apoptosis of HL-60 cells induced with VP-16 treatment, HL-60 cells were first incubated with rhGM-CSF before they were treated with VP-16. The apoptosis processes and the changes in apoptosis related gene bcl-2 and fas expression were observed. The morphological and ultrastructural changes were observed under optics microscope and electromicroscope. DNA fragmentation were detected by agarose gel electrophoresis, the apoptotic rate, bcl-2 and fas expression with flow cytometry. Our results showed that rhGM-CSF inhibited the apoptosis of HL-60 cells induced with VP-16 treatment, which enhanced the down-regulation of bcl-2 expression, but inhibited the up-regulation of fas expression. So it suggested that rhGM-CSF can decrease the sensitivity of HL-60 cells to VP-16, probably by down-regulation of fas expression.
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PMID:[Effects of rhGM-CSF on Apoptosis of HL-60 Cells Induced with VP-16 Treatment] 1257 65

Apoptosis is a physiological process by which multicellular organisms eliminate superfluous cells. Alterations in apoptosis play a key role in tumour development. The objective was to evaluate the immunohistochemical expression of p53, p21, bax, bak, fas, bcl-2 and bcl-x proteins in 10 endometriomas, 20 benign ovarian tumours (10 mucinous, 10 serous) and 30 malignant ovarian tumours (9 mucinous, 19 serous; 2 endometrioids). p53 positive cells (mean+/-SD) in endometriomas, and benign and malignant tumours were 1.9+/-3.2, 0 and 16.2+/-33.0, respectively. The difference was significant between benign tumours and endometriomas (P=0.003) but not between endometriomas and malignant tumours. P21 expression in endometriomas and benign and malignant tumours was 19.5+/-27.8, 1.7+/-6.7 and 4.1+/-8.6, respectively. Increased p21 expression was found in endometriomas compared with benign (P=0.001) and malignant (P=0.01) tumours. Bax expression was higher in endometriomas than in benign tumours (P=0.01), but no difference was found between endometriomas and malignant tumours. No difference in bak, fas, bcl-2 or bcl-x expression was observed among the groups. In endometriomas, a negative correlation was found between p53 and fas expression (P=0.04, r=0.66). Although endometriomas have histological features of benign ovarian tumours, endometriomas share with malignant ovarian tumours certain alterations in apoptosis-related proteins.
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PMID:Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours. 1275 64

Apoptosis is a physiologic process that deletes unwanted cells without inducing an inflammatory reaction. Survival of endometriotic implants is associated with decreased apoptosis and an inflammatory environment. The most widely accepted theory-transplantation theory-related to the pathogenesis of endometriosis is supported by the description of abnormal survival of regurgitated endometrial cells. Eutopic endometrial cells from women with endometriosis also seem to resist apoptosis further when compared with cells from disease-free women. Several apoptotic pathways have been studied. Recent literature concerning apoptosis-related genes such as bcl-2/bax and fas/fas ligand is summarized in this article. Special emphasis is placed on sex steroid modulation and cell adhesion regulation, both relevant in early events of endometriosis.
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PMID:Apoptosis and the pathogenesis of endometriosis. 1291 86

Glucose is the brain's major energy source; therefore, loss of neuronal cells is a potential consequence of hypoglycaemia. Since apoptosis is a major mechanism of neuronal loss following a range of insults, we explored potent anti-apoptotic systems (IGF-I and bcl-2) as means of enhancing neuronal survival in the face of glucose deprivation. Human neuroblastoma cells (SH-SY5Y, SHEP and SHEP-bcl-2) were exposed to low glucose as a model of glucopenia-induced neuronal damage. Administration of IGF-I and/or over-expression of the survival gene bcl-2 were exploited to attempt to limit neuronal loss. Neuronal survival mechanisms and interactions between these systems were investigated. Low glucose (0.25-2.5 mM) adversely affected cell growth and survival; however, IGF-I ameliorated these outcomes. Over-expression of bcl-2 blunted low glucose-induced apoptosis and up-regulated IGF-I receptor, with the effect of IGF-I addition being negligible on apoptosis, while significantly enhancing mitochondrial activity. In SH-SY5Y cells, IGF-I significantly changed >two-fold mRNA levels of the apoptosis-related genes gadd45, fas, iNOS, NFkB, TRAIL, without further affecting bcl-2 expression. In low glucose, IGF-I acutely enhanced glucose transport and translocation of GLUT1 protein to the cell membrane. GLUT1 mRNA expression was up-regulated by both IGF-I and bcl-2. The potent anti-apoptotic systems IGF-I and bcl-2 are both thus able to enhance cell survival in a glucose-deprived human neuronal model. Although we clearly show evidence of positive cross-talk via bcl-2 modulation of IGF-I receptor, IGF-I also has enhancing effects on mitochondrial function outside the bcl-2 pathway. The common effect of both systems on enhancement of GLUT-1 expression suggests that this is a key mechanism for enhanced survival. These studies also point to the potential use of IGF-I therapy in prevention or amelioration of hypoglycaemic brain injury.
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PMID:Neuronal protection from glucose deprivation via modulation of glucose transport and inhibition of apoptosis: a role for the insulin-like growth factor system. 1512 May 82

Molecular studies of brain tumors have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting clinical outcome and response to treatment. Quantitation of apoptosis by various techniques and the expression of several apoptotic markers have been studied in brain tumors, seeking to refine the information gained from established prognostic variables, which traditionally dictate therapeutic approaches. In the present review we discuss the role of the most extensively examined molecules involved in the apoptotic procedure, such as bcl-2, bax, fas/fasL, survivin and p53, as well as the incidence of baseline apoptosis in various brain tumors, in relation to prognosis. Summarizing current evidence, increased apoptosis and p53 genetic alterations have been advanced as adverse prognosticators in various types of central nervous system neoplasms, while bcl-2 expression appears to be deprived of any predictive value in primary brain tumors. The prognostic significance of the remaining apoptosis-related molecules remains controversial or too limited to draw any firm conclusions. The lack of unanimity of results mostly based on single-center retrospective studies underscores the necessity for large prospective randomized clinical trials, to elucidate the role of these molecular markers as determinants of clinical decision-making and as potential correlates of a pathobiologically tailored and individualized treatment strategy.
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PMID:Apoptotic markers for primary brain tumor prognosis. 1592 95

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Apoptosis, a physiological process by which multicellular organisms eliminate superfluous cells, is altered in tumor tissue. Here we studied the expression of the apoptosis-related proteins p53, bcl-2, bax, p21 and fas in proliferative (n=9) and secretory (n=9) endometrium, and in peritoneal (n=11), ovarian (n=20) and colorectal (n=20) endometriosis, by qualitative and semi-quantitative immunohistochemical methods using the percentage of positive cells and HSCORE analysis. In endometrium, p53, p21 and fas expression was low, whereas bax and bcl-2 expression was elevated. Using HSCORE analysis, only bcl-2 expression varied during the menstrual cycle (48.9+/-34.2% in the proliferative phase, 11.5+/-24.7% in the secretory phase, p=0.01). Using HSCORE analysis, p53 expression was higher in ovarian endometriosis than in peritoneal (p<0.0001) and colorectal endometriosis (p=0.03). P21 expression was higher in ovarian endometriosis than in peritoneal (p=0.01) and colorectal endometriosis (p=0.01). Bcl-2 expression was lower in ovarian endometriosis than in peritoneal (p=0.0002) and colorectal endometriosis (p<0.0001). Fas expression was higher in peritoneal endometriosis than in ovarian (p=0.02) and colorectal endometriosis (p=0.008). In conclusion, these results confirm the involvement of apoptosis in the pathogenesis of endometriosis. Moreover, expression of apoptosis-related proteins varies according to the location of endometriosis suggesting the involvement of different apoptotic pathways.
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PMID:Expression of apoptosis-related proteins in peritoneal, ovarian and colorectal endometriosis. 1637 43

The present study aimed to find out dynamic changes of apoptosis in human cytomegalovirus (HCMV) infected cells and the influence of HCMV infection on activation of caspase-3 and the expression of apoptosis-regulating genes, bcl-2 and fas mRNA. The sequential changes of apoptotic cell rate in high and low MOI (MOI = 2.5 and 0.25 respectively) of HCMV infected human embryonic lung fibroblasts (HELFs) at 1 h, 12 h, 24 h, 36 h, 48 h, 72 h and 96 h post-infection were measured by flow cytometry. The expression levels of caspase-3 protein and bcl-2 and fas mRNA in HCMV infected cells (MOI = 0.25) at 72 h post-infection were detected by Western blot and in situ hybridization methods, respectively. It was found that the ratio of apoptotic cells in normal controls was consistently lower, but the rates in low and high MOI infected cells were gradually increased with time prolonged, reached peak at 96 h (8.85%) and 72 h (25.63%), respectively. By Western blot analysis, only a narrow band of 32 kD (1 kD = 0.992 1 ku) procaspase-3 was found in normal cells, but a wider procaspase-3 band and a much wider band of 17 kD proteins (p17) appeared in the infected cells. Meanwhile, the expression of bcl-2 mRNA was higher and that of fas mRNA was lower in the normal HELF cells, whereas there were significantly lower bcl-2 mRNA and higher fas mRNA expression levels in HCMV infected cells. It was concluded that HCMV was a stronger inducer of apoptosis in HELF cells. Caspase-3, as the marker of undergoing apoptosis, was expressed increasingly and activated in the infected cells, indicating its action in HCMV-inducing apoptosis. Down-regulating bcl-2 mRNA expression and up-regulating fas mRNA expression were also involved in the mechanism of HCMV-induced apoptosis.
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PMID:Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors. 1646 50

Interleukin-6 (IL-6) has been shown to rescue enterocytes from hypoxia-induced apoptosis when given orally following hemorrhagic shock. In vitro models using an intestinal epithelial cell line (IEC-6) cultured with lipopolysaccharide (LPS) under low O2 conditions, to mimic intestinal conditions, show that these cells also undergo apoptosis, which can be reduced by subsequent culture with IL-6. To examine further the mechanisms of rescue, we cultured normal rat intestinal epithelial cells (IEC-6) under both normoxic and hypoxic conditions and analyzed their responses to LPS and IL-6. We showed that IEC-6 expressed IL-6 receptor on its surface. Further, IEC-6 cells could be rescued from hypoxia-induced apoptosis by co-culture with IL-6. RNase protection assay (RPA) examination revealed that under hypoxic conditions, IEC-6 cells that were resistant to apoptosis showed reduced fas expression and increased bcl-2 expression after co-culture with LPS+IL-6.
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PMID:IL-6 protects enterocytes from hypoxia-induced apoptosis by induction of bcl-2 mRNA and reduction of fas mRNA. 1687 Jan 48

Recent data suggest that new treatment options for superficial bladder cancer are necessary, owing to the high recurrence rate after conventional treatment, especially in T1G3 and Bacillus Calmette-Guerin-refractory patients. Phase I and II studies have demonstrated that gemcitabine may represent a candidate for intravesical therapy in superficial bladder cancer. Despite clinical trials, the in-vitro cytotoxic and proapoptotic effects of gemcitabine have been poorly investigated. In the present study, we investigated how gemcitabine affects apoptosis in bladder cancer cell line 5637, which has the same molecular features of high-risk superficial bladder cancer. Apoptosis was evaluated by DNA fragmentation, flow cytometry and caspase activation. bcl-2, bcl-X, bax, survivin and fas gene expression were also evaluated by reverse-transcriptase polymerase chain reaction. Nuclear factor-kappa B activation was assessed by immunofluorescence. Gemcitabine induced apoptosis in 5637 cells in a time-dependent manner, with activation of caspase-3, -8 and -9. Expression of bcl-2, bax, survivin and bcl-X was not affected by treatment, whereas fas strongly increased after 24 h of treatment. After treatment, we failed to find any nuclear localization of nuclear factor-kappa B. As gemcitabine-induced apoptosis involves fas upregulation, these results may encourage the investigation of intravesical gemcitabine in fas-negative bladder tumors. Furthermore, as nuclear factor-kappa B activation by cisplatin, doxorubicin and adriamycin may result in enhanced proliferation, migration, immortality and inhibition of apoptosis, the observation that gemcitabine does not activate nuclear factor-kappa B may have implications in intravesical therapy of high-risk superficial bladder cancer.
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PMID:Gemcitabine-induced apoptosis in 5637 cell line: an in-vitro model for high-risk superficial bladder cancer. 1715 4


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