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 expression of the proto-oncogene bcl-2, whose main function appears to be an inhibition of apoptosis, was investigated in 164 cases of primary small cell lung cancer by means of immunohistochemistry in a retrospective analysis. One-hundred twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference in serum LDH levels and proliferative activity between the two groups. An analysis revealed a median survival time of 12 months for patients with bcl-2 positive tumors compared to 9.5 months for patients with bcl-2 negative tumors. Although statistical significance is not achieved, there is a trend towards longer survival in patients whose tumors express bcl-2. This tendency is also reflected by a higher rate of complete remission after chemotherapy: 40% in patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In multivariate analysis, tumor stage followed by Karnofsky index were the most valuable predictors for complete remission. LDH and tumor stage were most predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may reflect a less aggressive mechanism of transformation and a higher susceptibility to cytostatic treatment.
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PMID:Expression of bcl-2--protein in small cell lung cancer. 886 21

Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X(L), Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X(L) were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X(L). Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X(L) tended to be expressed in samples from cases at advanced clinical stage. Bcl-X(L) was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X(L) and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X(L) although Bcl-X(L) tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X(L) and Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.
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PMID:Expression of Bcl-2 family of proteins in fresh myeloma cells. 982 59

Oxidized low density lipoproteins (OxLDLs) are believed to play a central role in atherogenesis and to possess a wide variety of biological properties; among them, OxLDLs are cytotoxic to cultured vascular cells in that they induce necrosis and apoptosis. Moreover, OxLDLs are known to induce the expression of heat shock protein 70 (Hsp70), a protein that protects cells from several cytotoxic stimuli. To determine whether Hsp70 can protect cells against OxLDL-induced cytotoxicity, COS-1 cells were transfected with a construct containing human Hsp70. A number of cell lines permanently expressing Hsp70 were obtained, 1 of which (cos-Hsp70/10, with high Hsp70 expression) was selected for further studies. Hsp70 overexpression protected cells from toxic stimuli, such as H(2)O(2), UV irradiation, and heat shock, suggesting that the overexpressed protein was functional. When incubated with OxLDLs, however, the clone overexpressing Hsp70 showed a significant decrease in viability, as determined by the [(3)H]adenine release assay (319.8+/-3.16% of control for transfected cells versus 217.6+/-6.08% for control cells exposed to 100 microgram protein/mL of OxLDL), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (12.5+/-0.9% versus 28.9+/-1.99% of control, respectively), and LDH release (48.4+/-0.04% versus 15.2+/-0.06% of control cells). The increased expression of BAX and the decreased expression of Bcl-2 (a proapoptotic and an antiapoptotic protein, respectively) in cos-Hsp70/10 cells and in control cells on incubation with OxLDLs suggested that overexpression of Hsp70 did not confer protection against apoptosis induced by OxLDLs. The analysis of nucleosome content and the nuclear staining with Hoechst 33258 confirmed this finding. These data suggest that overexpression of Hsp70 not only fails to protect COS-1 cells against OxLDL-induced apoptosis but rather confers a higher sensitivity to the cytotoxic action of these lipoproteins. Thus, the Hsp70 response, although induced by OxLDLs, cannot protect cells from lipoprotein toxicity.
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PMID:Overexpression of inducible heat shock protein 70 in Cos-1 cells fails to protect from cytotoxicity of oxidized ldls. 1123 13

The objective of this study was to characterize the role of Bcl-2 expression in Fas-mediated apoptosis in human renal cell carcinoma (RCC) cell lines. RT-PCR analyses showed that 10 different RCC cell lines expressed Fas, but not Fas ligand. Seven of 10 cell lines expressed Fas strongly, while 3 cell lines weakly expressed Fas by flow cytometric analyses. Measurement of the LDH concentration in the culture supernatant revealed that 6 of the 7 cell lines which expressed Fas strongly were sensitive to treatment with an agonistic anti-Fas monoclonal antibody (CH11), whereas all cell lines which weakly expressed Fas did not show Fas-mediated cell death. Furthermore, Bcl-2 expression was found only in three cell lines which were all susceptible to CH11, and the downregulation of Bcl-2 protein by treatment with antisense oligodeoxynucleotide targeting Bcl-2 gene resulted in an enhancement of cell death induced by CH11. These findings suggest that strong Fas expression is necessary for Fas-mediated cell death in RCC cell lines, and Bcl-2 has a protective role against treatment with an anti-Fas monoclonal antibody, despite the fact that Bcl-2 expression was observed only in sensitive cell lines to Fas-mediated cell death.
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PMID:Bcl-2 modulates Fas-mediated apoptosis in human renal cell carcinoma cell lines. 1135 Dec 49

Apoptosis in the testis represents an important physiological mechanism that regulates the number of germ cells in the seminiferous epithelium. This apoptosis is believed to be regulated by many factors, including growth factors and cytokines, which appear to suppress apoptosis of the germ cells. In this study, we examined the roles of Sertoli cells on the regulation of pachytene spermatocyte (PS) and round spermatid (RSd) apoptosis with either a co-culture trans-well system or a direct contact system. Apoptosis was detected by low molecular weight DNA fragmentation assay, in situ end labeling, and an LDH assay. In addition, the level of Bcl-2, Bax, and ICE mRNAs in PS and RSd by Northern blot analysis. When PS and RSd were cultured with Sertoli cells in either a trans-well system or direct contact system, the extent of apoptotic DNA fragmentation and LDH level were both significantly lower than those control values. TUNEL staining also revealed the inhibition of apoptosis of PS and RSd when they were cultured with Sertoli cells compared with controls (p <0.05). Moreover, the extent of apoptotic DNA fragmentation and LDH level were significantly lower in the direct contact system than in the trans-well system. TUNEL staining also demonstrated a more decrease in apoptosis of PS and RSd in the direct contact system compared with the trans-well system (p < 0.05). PS and RSd cultured with Sertoli cells exhibited an increase in Bcl-2 mRNA, whereas those cultured with serum-free medium did not show any change. The levels of Bax and ICE mRNAs decreased in PS and RSd cultured with Sertoli cells in comparison with control values. These results suggest that Sertoli cells can prevent apoptosis of germ cells, and that the effect of Sertoli cells on germ cells is mediated by cell to cell interaction or, remote effects of inhibitory factors on apoptosis.
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PMID:Sertoli cells inhibited apoptosis of pachytene spermatocytes and round spermatids. 1142 23

Cellular senescence may be an antioncogenic event. Bcl-2 is a product of the oncogene, bcl-2, but it may also participate in cellular senescence. To investigate the role of Bcl-2, we analyzed the level of Bcl-2 during aging of normal human fibroblasts by immunoblot analysis and found that its level was highly suppressed in four normal senescent fibroblast strains. This result suggests that senescent cells are more sensitive to induction of death than young cells. Nevertheless, senescent cells showed more resistance to death induced by hydrogen peroxide than young cells, according to LDH assay. Because the balance among antiapoptotic and proapoptotic proteins is an important factor for the determination of cell death, we examined levels of other Bcl-2 family and apoptosis-regulating proteins, but observed no reasonable change to explain the resistance. During the course of the death induction experiment, we obtained results showing that growth-arrested cells were also resistant to death, and this was further confirmed by a BrdU-labeling experiment. As senescent cells are stopped permanently in the G0/G1-phase of the cell cycle, our data strongly suggest that this is the cause of resistance to death in senescent cells.
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PMID:Senescent cells are resistant to death despite low Bcl-2 level. 1155 74

Estrogens possess neuroprotective and antiapoptotic properties, however, the issue of involvement of estrogen receptors (ER)-dependent genomic pathway in these effects still remains controversial. Moreover, the majority of data on antiapoptotic effects of estrogens concern non-neuronal cells. In the present study we compared effects of the potent ER agonist, estradiol-17beta (E2), and its metabolite with a weak affinity for ER, estriol, on the neurotoxicity induced by high (1 and 5 mM) NMDA concentrations and on the apoptosis induced by low (0.1 mM) concentration of NMDA in rat primary cortical neurons. The obtained data showed that 24-hour exposure of cortical neurons to NMDA (0.1-5 mM) resulted in a dose-dependent increase in LDH level. Twenty four-hour pretreatment with estriol (100 nM and 500 nM) reduced the NMDA (1 and 5 mM)-induced toxicity by 16-26%, while estradiol-17beta (500 nM) reduced NMDA (5 mM)- induced toxicity by 14%. Twenty four hour exposure of cortical neurons to NMDA (0.1 mM) resulted in decrease of the level of antiapoptotic protein - Bcl-2 by 60% and increased the number of apoptotic cells by 50% compared to the control. Twenty four hour pretreatment with estradiol-17beta or estriol (100 and 1000 nM) prevented the NMDA-induced apoptotic changes. The specific estrogen receptor antagonist ICI 182,780 (100 nM) had no effect alone and did not antagonize the effects of estrogens on NMDA-induced toxicity as well as on changes in Bcl-2 level. The higher efficacy of estriol, together with the fact that the specific ER receptor antagonist, ICI 182,780, did not inhibit the above-described effects support the hypothesis about a nongenomic mechanism of the anti-NMDA action of estrogens.
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PMID:Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis in primary cultures of rat cortical neurons. 1159 61

Two diterpenoids, oridonin (1) and ponicidin (2), were isolated from the 95% ethanol extract of Rabdosia rubescens and were evaluated for antiproliferative activity on cancer cells and human peripheral blood mononuclear cells (PBMC) in vitro. Oridonin has much more potent cytotoxic effects on four tumor cells (human melanoma A375-S2, human cervical cancer HeLa, human breast adenocarcinoma MCF-7, murine fibrosarcoma L929) than does ponicidin. The growth-inhibitory activity of oridonin for A375-S2 cells was more potent than that for the other cell lines, with an IC50 of 15.1 +/- 1.2 micromol L(-1). Treatment with oridonin (34.3 micromol L(-1)) for 12 h significantly inhibited A375-S2 cell growth, and showed weaker cytotoxicity against PBMC. By contrast, ponicidin markedly inhibited the growth of PBMC under the same conditions. When caspases-3 and -8 were activated at early stages after treatment of A375-S2 cells with oridonin (34.3 micromol L(-1)), apoptotic bodies were formed, nuclear damage was observed by Hoechst 33258 staining and DNA fragmentation was exhibited. In addition, oridonin increased the expression of the apoptosis inducer, Bax, promoted the release of cytochrome c without affecting Bcl-2 expression, and activated down-stream caspase-9 in the mitochondrial pathway. These observations indicated that an appropriate dose of oridonin gave an initial premitochondrial phase that involved the Bcl-2 family of the pro-apoptotic protein Bax that required the participation of caspase-9 and caspase-3. However, on treatment with oridonin (137.4 micromol L(-1)) for 12 h, the majority of A375-S2 cells underwent necrosis as measured by an LDH activity-based assay. Our results suggest that oridonin induces A375-S2 cell death on the balance of apoptosis and necrosis.
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PMID:Oridonin induced A375-S2 cell apoptosis via bax-regulated caspase pathway activation, dependent on the cytochrome c/caspase-9 apoptosome. 1500 59

Our previous report has showed that the treatment of 48 h with 22 mM glucose prevents hypoxia-induced cardiac cell death. In the present study, we investigated whether high glucose affects the mitochondrial death pathway during hypoxia, and if it does, what relates to the high glucose induced cardioprotection. Heart-derived H9c2 cells were incubated in low (5.5 mM) or high (22 mM) glucose medium for 48 h, then transferred to a normoxic or hypoxic condition. The hypoxia-induced reduction of mitochondrial redox potential, assessed by MTT assay, was inhibited in high glucose treated cells. The mitochondrial membrane potential was significantly decreased by hypoxia in low glucose treated cells, but not in high glucose treated cells. The hypoxia-induced cytoplasmic accumulation of cytochrome c, released from the mitochondria, was blocked by a treatment of high glucose. High glucose did not induce the expression of an antiapoptotic protein Bcl-2, nor did it reduce a proapoptotic protein Bax, but it did inhibit a hypoxia-induced downregulation of Bcl-2. The cellular ATP contents were not changed by the treatment of high glucose for 48 h, and the hypoxia-induced decline of intracellular ATP level was observed in high glucose treated cells and in low glucose. A glycolytic inhibitor, 2-deoxyglucose, did not reverse the high glucose induced reduction of LDH release. The elevation of [ROS](i) induced by hypoxia was inhibited in high glucose treated cells. These results suggest that high glucose induced cardioprotection may be accounted for in part by the preservation of MMP and the maintenance of a basal level of [ROS](i) during hypoxia.
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PMID:High-glucose induced protective effect against hypoxic injury is associated with maintenance of mitochondrial membrane potential. 1503 43

Although injury of epithelial cells has been reported to be responsible for renal disease such as acute renal failure, its molecular mechanisms are largely unknown. As hypoxia has been postulated as the initial trigger of epithelial injury, we studied the molecular mechanisms of apoptosis induced by hypoxia in human renal epithelial cells. Severe hypoxia caused epithelial cell death, accompanied by a significant increase in LDH release (p<0.01). In addition, hypoxic treatment of epithelial cells resulted in a significant increase in apoptotic cells as assessed by cell morphology (p<0.01). The apoptotic change in epithelial cells under hypoxic condition was also confirmed by a significant increase in caspase-3-like activity and release of cytochrome c (p<0.01). The decrease in epithelial cell number was completely abolished by addition of a wide-spectrum caspase inhibitor, Z-VAD, rather than Z-DEVD, a specific caspase-3 inhibitor (p<0.01). Thus, we further studied the molecular mechanisms of apoptosis induced by hypoxia. Anti-apoptotic factors, Bcl-2 and Bcl-xL, were significantly decreased in epithelial cells under a hypoxic condition as assessed by Western blotting (p<0.01). In contrast, hypoxia did not alter their location. Of particular importance, translocation of a proapoptotic factor, Bax, from the cytoplasm to the mitochondrial membrane was observed in response to hypoxia, whereas total Bax protein was not changed by hypoxia. Overall, this study demonstrated that hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. The pro-apoptotic mechanisms of hypoxia in epithelial cells largely depend on a significant decrease in Bcl-2 and Bcl-xL. In addition, the present results demonstrate that translocation of Bax from the cytosol to the mitochondrial membrane occurred under hypoxia, thereby leading to pathological tissue destruction.
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PMID:Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury. 1537 94


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