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 transmembrane transport pump P-glycoprotein (P-gp) causes the efflux of chemotherapeutic agents from cells and is an important system that secures multidrug resistance (MDR) of neoplastic cells. In the present study drug sensitive L1210 and multidrug resistant L1210/VCR mouse leukemic cell lines were used as an experimental model. We found that LY 294,002, a specific inhibitor of PI3K/Akt kinase pathway, reduced the degree of vincristine resistance in L1210/VCR cells significantly and in a concentration-dependent manner. This was accompanied by decrease in IC(50) value to vincristine from 3.195+/-0.447 to 1.898+/-0.676 micromol/l for 2 micromol/l, to 0.947+/-0.419 micromol/l for 4 micromol/l, and to 0.478+/-0.202 micromol/l for 8 micromol/l LY294,002. The IC(50) value of sensitive cells for vincristine was about 0.010 micromol/l. FACS analysis of the proportion of cells in apoptosis or necrosis by annexin-V apoptosis kit showed the following: (i) vincristine-induced apoptosis in resistant cell to a much lower extent than in sensitive cells; (ii) LY294,002 alone did not induce apoptosis or necrosis in both sensitive and resistant cells; (iii) LY294,002 applied together with vincristine significantly increased the number of apoptotic cells. Transport activity of P-gp in resistant cells was monitored using calcein/AM as substrate and was depressed by LY294,002 in a concentration dependent manner. Significant differences in calcein retention were not observed when cells were preincubated with LY294,002 at different times from 0.5 to 24h. Sensitive and resistant cells contain similar amounts of uncleaved (i.e., unactivated) caspase-3 but in latter cells the activation of caspase-3 by proteolytic cleavage was decreased. The reversal of vincristine resistance by LY294,002 was associated with marked activation of caspase-3. Western blot analysis revealed that the development of MDR phenotype in L1210/VCR cells was also associated with increased level of Bcl-2 protein. All the above findings point to the possible involvement of PI3K/Akt kinase pathway in modulation of P-gp mediated multidrug resistance in L1210/VCR mouse leukemic cell line. MDR reversal effect of LY294,002 is accompanied with this compound's influence on vincristine-induced apoptosis.
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PMID:LY294,002, a specific inhibitor of PI3K/Akt kinase pathway, antagonizes P-glycoprotein-mediated multidrug resistance. 1701 May 77

Monosodium glutamate (MSG), the sodium salt of glutamate, is commonly used as a flavor enhancer in modern nutrition. Recent studies have shown the existence of glutamate receptors on lymphocytes, thymocytes and thymic stromal cells. In this study, we evaluated the in vitro effect of different MSG concentrations on rat thymocyte apoptosis and expression of two apoptosis-related proteins, Bcl-2 and Bax. Rat thymocytes, obtained from male Wistar rats, were exposed to increasing concentrations of MSG (ranging from 1 mM to 100 mM) for 24 h. Apoptosis was detected using the Annexin V-FITC/PI apoptosis detection kit and cells were analyzed using a flow cytometer. Expression of Bcl-2 and Bax proteins were determined with flow cytometry using respective monoclonal antibodies. Exposure to MSG resulted in a dose-dependent decrease in cell survival (as determined by trypan blue exclusion method). Annexin V-FITC/PI also confirmed that MSG increased, in a dose-dependent manner, apoptotic cell death in rat thymocyte cultures. MSG treatment induced downregulation of Bcl-2 protein, while Bax protein levels were not significantly changed. Our data showed that MSG significantly modulates thymocyte apoptosis rate in cultures. The temporal profile of Bcl-2 and Bax expression after MSG treatment suggests that downregulation of Bcl-2 protein and the resulting change of Bcl-2/Bax protein ratio may be an important event in thymocyte apoptosis triggered by MSG.
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PMID:Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat thymocyte culture. 1718 47

We assessed molecular markers such as BRCA1, K-ras, p53, Bcl-2, Bcl-XL, Survivin and telomerase activity in untreated ovarian cancer tissue samples, ascitic cells and normal ovarian tissues and gathered insights into their correlation with each other and also with apoptotic index. The expression of these proteins was analyzed by Western blotting and immunohistochemistry. Apoptotic index was determined by TUNEL assay and telomerase activity was measured by PCR-ELISA kit. p53, Bcl-2, Bcl-XL, K-ras and Survivin were found to be over expressed in tumors and ascitic cells as compared to normal controls whereas there was no significant difference in expression of BRCA1. A significantly higher telomerase activity and lower apoptotic index in tumors as compared to controls was observed. p53 positively correlated with Bcl-2, Bcl-XL, K-ras and Survivin expression and also clinical stage of the disease. A positive correlation between Survivin and Bcl-2, Bcl-XL was seen. Apoptotic Index, telomerase activity and BRCA1 expression showed no correlation with any of the parameters. Our study confirms the fact that multiple gene interactions govern the pathogenesis of ovarian cancer, and analyzing ascitic cells of ovarian cancer patients may help to delineate molecular profile of the primary tumor.
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PMID:Role of apoptotic regulators in human epithelial ovarian cancer. 1761 99

This study is to investigate if madecassoside can protect against myocardial reperfusion injury in rabbit heart in vivo. The ischemia reperfusion model was established. Left ventricular function and ECG were monitored at the ischemia and reperfusion period. The infarct areas were expressed as percentage. The levels of LDH, CK, MDA and SOD were measured and C-reactive protein (CRP) in serum was measured by ELISA kit. Cardiomyocyte apoptosis were measured by TUNEL staining. A monoclonal rabbit anti-goat Bcl-2 proteins as primary antibody was used for Bcl-2 immunohistochemical staining. Treatment with madecassoside (3.2, 1.6 and 0.8 mg x kg(-1)) i.v. during ischemia reperfusion injury attenuated myocardial damage, that is, characteristic of decreasing infarct size, decreasing LDH and CK release. Activities of SOD were diminished and MDA level increased obviously in control group whereas pretreatment with madecassoside significantly blunted the decrease of SOD activity, markedly reduced the levels of MDA, CRP and cardiomyocyte apoptosis, and upregulated the expression of Bcl-2. Madecassoside has the protective effect against myocardial ischemia reperfusion injury, and effects of anti-lipid peroxidation, enhancement of SOD activity, anti-inflammation and anti-apoptosis.
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PMID:[Protective effect of madecassoside against reperfusion injury after regional ischemia in rabbit heart in vivo]. 1770 67

To investigate the correlation between sensitivity to Fas ligand (FasL) and expression level of decoy receptor 3 (DcR3) on tumor cell surface, Fas/DcR3 mRNA expression was detected by RT-PCR. Anti-DcR3 mAb was used to detect expression level of DcR3 on surface of tumor cells by flow cytometry. Caspase-8, caspase-9, caspase-3, Bcl-2 expressions were analyzed by Western blot, respectively. Sensitivity to apoptosis induced by FasL was determined by Annexin V apoptosis kit. The expressions of DcR3 on the surface of tumor cells from high to low were approximately 35.3% in BGC823 cells, and 21.6% in MCF-7 cells, respectively. The apoptotic rates induced by FasL from low to high were 15.6% in BGC823 cells, and 58.2% in MCF-7 cells, respectively. There was a significant correlation between the expression levels of DcR3 with FasL-inducing apoptosis.
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PMID:Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. 1816 57

This study examined the effects of arsenic trioxide on apoptosis and interleukin-4 release in T cells of asthmatic patients in vitro and investigated the role of Bcl-2 in the active mechanism. T cells were isolated from asthmatic patients (n = 21) and healthy controls (n = 20), and then treated with arsenic trioxide and dexamethasone. Cell apoptosis was measured using fluorescence microscopy, flow cytometry and a cytochrome c ELISA kit. Interleukin-4 levels in the serum and in supernatants from T cells were quantified by ELISA. Flow cytometric analysis and immunofluorescence studies were performed to determine Bcl-2 expression. T cells of the asthmatic patients (i. e. without treatment) exhibited decelerated spontaneous apoptosis after 24 h incubation in vitro when compared to T cells of the healthy controls. With dexamethasone treatment, an increase in apoptosis of T cells was not significantly different between both groups, irrespective of the method used. Arsenic trioxide treatment, however, significantly increased the apoptosis of T cells of the asthmatic group and showed a slight effect on the control group. In asthmatic patients, elevated levels of interleukin-4 and up-regulated Bcl-2 expression were detected. Moreover, in vitro, T cells of asthmatic patients spontaneously released more interleukin-4 and exhibited more Bcl-2 expression than T cells from the control group. Arsenic trioxide treatment significantly decreased interleukin-4 release and down-regulated Bcl-2 expression in asthmatic patients, while it only slightly affected healthy controls. Dexamethasone treatment decreased interleukin-4 release in both groups examined. It did not significantly influence Bcl-2 expression. These results suggest that arsenic trioxide induces T cell apoptosis and decreases interleukin-4 release in T cells of asthmatic patients in vitro and that down-regulation of Bcl-2 expression may be an important mechanism.
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PMID:In vitro arsenic trioxide induces apoptosis in T cells of asthmatic patients by a Bcl-2 related mechanism. 1835 29

Intestinal lymphangiectasia is a rare condition, which is characterized by the dilation of small bowel lymphatics and presents with signs and symptoms of protein-losing enteropathy. Some patients have complained of occlusive symptoms attributable to the mechanical obstruction caused by the considerable mucosal edema associated with the lymphatic dilation. On the basis of the hypothesis that alterations in the neuromuscular structures controlling clearance function or gut tone may play a role in ileal dilation, we examined the resected ileum of a 48-year-old male patient with segmental lymphangiectasia histologically, immunohistochemically (for S100 protein, PGP 9.5, Bcl-2, neuron-specific enolase, neurofilaments, synaptophysin, and CD117/C-kit), and by means of electron microscopy. Histology showed pseudocystic dilation of the mucosal, submucosal, and muscular lymphatics with fragmentation of the circular and longitudinal muscle layers. Hardly any neural expression of synaptophysin was observed, but the neural structures were otherwise morphologically normal and reacted normally to the other neural markers. This case shows that neuromuscular alterations can be found in the dilated ileum of patients with segmental lymphangiectasia.
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PMID:Neuromuscular alterations in the dilated ileum of an adult patient with segmental lymphangiectasia. 1879 10

Hydroxysafflor yellow A (HSYA), is a component of the flower, Carthamus tinctorius L. In this study, we investigated its effect on Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia. We evaluated cell viability using the MTT kit. The cell cycle distribution was analyzed by PI staining flow cytometric analysis. PI AnnexinV-FITC detection and the TUNEL assay were performed to evaluate the apoptosis rate. Nitric oxide (NO) generation in cell supernatant was measured by the Griess assay. RT-PCR, Western blot and Immunocytochemistry analysis were used to evaluate the changes of Bcl-2, Bax, p53 and eNOS. Our data showed that HSYA inhibited cell apoptosis and cell cycle G1 arrest induced by hypoxia. HSYA treatment increased the Bcl-2/Bax ratio of protein and mRNA, reduced p53 protein expression in cell nucleus. In addition, HSYA enhanced the NO content of cell supernatant under hypoxia, accompanied with upregulating eNOS mRNA expression and protein level. Taken together, these results demonstrate that HSYA could protect HUVECs from hypoxia induced injuries by inhibiting cell apoptosis and cell cycle arrest. These findings have partly revealed the molecular mechanism of HSYA on treating of ischemic heart disease. We expected our experiments might provide some clues for further research.
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PMID:Effect of Hydroxysafflor yellow A on human umbilical vein endothelial cells under hypoxia. 1908 79

We evaluated the expression of molecular markers in colorectal adenocarcinoma in relation to p53 protein expression. Tissue samples of 54 patients with colorectal adenocarcinoma were obtained at surgery at university hospitals in the years 2000-2003. These were analyzed by immunohistochemical techniques using primary antibodies for p53, Bcl-2, P-gp, topoisomerase II alpha and Thymidylate Synthase (TS), thymidine phosphorylase/PD- ECGF (TP) and LSAB detection kit. The highest prevalence of expression among six analyzed markers were P-gp and p53 with 77% expression and the lowest one was Topo II with 35% expression. No clinicopathological significance was recorded in colorectal cancer patients. Several immunophenotypes were observed between p53 and other molecular markers. Additionally the prevalence of lack of expression of Bcl-2, Topo II and TS was higher in p53+ tumors than in p53-tumors. A significant association (p = 0.021) existed between p53/Bcl-2 coexpression and mean age of patients (63.5 [10.1]y vs. 52.3 [15.2] y) and between p53/TP coexpression and sex (66.7% male; (p = 0.022). Overexpression of mutated p53 seen in tumor samples may alter the expression pattern of other molecular markers that are predictors of tumor response to chemotherapy regimens. Age and sex of patients could also affect the p53 related proteins such as Bcl-2 and TP, which can affect therapeutic outcome and disease prognosis. These findings emphasize the importance of tumor immunophenotypes as valuable prognostic or predictive markers in clinical settings.
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PMID:Association between p53 expression and Bcl-2, P-glycoprotein, topoisomerase II alpha, thymidylate synthase and thymidine phosphorylase as potential therapeutic targets in colorectal cancer patients. 1909 Jan 49

Matrix metalloproteinase (MMP) family member matrilysin (matrilysin) has been indicated to induce apoptosis-resistance and chemoresistance. The purpose of current study was to investigate the potential capacity of induction cisplatin-resistance upon the unremitting exposure to exogenic matrilysin. At the same time, the expressions of apoptosis-related genes were examined to clarify the underlying mechanisms. A549 lung adenocarcinoma cells was used to establish our chronic exposure models. The viability of A549 lung adenocarcinoma cells was determinated by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, immunocytochemistry staining and real-time quantitative RT-PCR, respectively. Overall, chronic exposure to crescenting level of exogenous matrilysin (10, 50, 100, 200 ng/ml) did not significantly alter the growth rates of A549 cells. However, a certain range of matrilysin might protect tumor cells from cisplatin-medicated death. The underlying mechanism may due to the Bcl-2 overexpression and imbalance in the ratio of Bcl-2/Bax. Our results offer a potential mechanism to explain the impact of matrilysin on apoptosis and provide new insights into the profound mechanisms of acquired cisplatin-resistance. Further researches are highly suggestive of this association which has great clinical implications.
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PMID:Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl-2 expression in A549 lung adenocarcinoma cells. 1910 75


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