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)

Flavonoids were demonstrated to possess several biological effects including antitumor, antioxidant, and anti-inflammatory activities in our previous studies. However, the effect of glycosylation on their biological functions is still undefined. In the present study, the apoptosis-inducing activities of three structure-related flavonoids including aglycone quercetin (QUE), and glycone rutin (RUT; QUE-3-O-rutinoside), and glycone quercitrin (QUI; QUE-3-O-rhamnoside) were studied. Both RUT and QUI are QUE glycosides, and possess rutinose and rhamnose at the C3 position of QUE, respectively. Results of the MTT assay showed that QUE, but not RUT and QUI, exhibits significant cytotoxic effect on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, apoptotic bodies, and an increase in hypodiploid cells by flow cytometry analysis. QUE, but not RUT or QUI, caused rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase (PARP) and D4-GDI proteins, and the appearance of cleaved caspase 3 fragments being detected in QUE- but not RUT- or QUI-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in QUE-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bag remained unchanged. The caspase 3 inhibitor, Ac-DEVD-FMK, but not the caspase 1 inhibitor, Ac-YVAD-FMK, attenuated QUE-induced cell death. Results of DCHF-DA assay indicate that no significant increase in intracellular peroxide level was found in QUE-treated cells, and QUE inhibited the H(2)O(2)-induced intracellular peroxide level. Free radical scavengers N-acetyl-cysteine (NAC) and catalase showed no prevention of QUE-induced apoptosis. In addition, QUE did not induce apoptosis in an mature monocytic cell line THP-1, as characterized by a lack of DNA ladders, caspase 3 activation, PARP cleavage, and an Mcl-1 decrease, compared with those in HL-60 cells. Our experiments provide evidence to indicate that the addition of rutinose or rhamnose attenuates the apoptosis-inducing activity of QUE, and that the caspase 3 cascade but not free radical production is involved.
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PMID:Differential apoptosis-inducing effect of quercetin and its glycosides in human promyeloleukemic HL-60 cells by alternative activation of the caspase 3 cascade. 1287 37

Mammalian tRNA 3' processing endoribonuclease (3'-tRNase) can cleave any RNA at any site under the direction of small guide RNA (sgRNA) in vitro. sgRNAs can be as short as heptamers, which are much smaller than small interfering RNAs of approximately 21 nt. Together with such flexibility in substrate recognition, the ubiquity and the constitutive expression of 3'-tRNase have suggested that this enzyme can be utilized for specific cleavage of cellular RNAs by introducing appropriate sgRNAs into living cells. Here we demonstrated that the expression of chloramphenicol acetyltransferase can be downregulated by an appropriate sgRNA which is introduced into Madin-Darby canine kidney epithelial cells as an expression plasmid or a synthetic 2'-O-methyl RNA. We also showed that 2'-O-methyl RNA heptamers can attack luciferase mRNAs with a high specificity and induce 3'-tRNase-mediated knock-down of the mRNAs in 293 cells. Furthermore, the MTT cell viability assay suggested that an RNA heptamer can downregulate the endogenous Bcl-2 mRNA in Sarcoma 180 cells. This novel sgRNA/3'-tRNase strategy for destroying specific cellular RNAs may be utilized for therapeutic applications.
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PMID:Intracellular mRNA cleavage by 3' tRNase under the direction of 2'-O-methyl RNA heptamers. 1288 94

To investigate the inhibiting effect of arsenic trioxide (As(2)O(3)) on the telomerase activity of leukemia cell lines NB4 and Jurkat cells, MTT assay, electrophoresis of genomic DNA, protein/DNA dual parameter flow cytometry as well as a semi-quantitative telomeric repeat amplification protocol (TRAP) assay and RT-PCR were used to examine the effect of As(2)O(3) on cell proliferation, telomerase activity and expression of cell cycle regulatory proteins. The results showed that cell proliferation and telomerase activity were significantly inhibited and apoptosis was induced in these cells after exposure to As(2)O(3). Furthermore, the expression of some cell cycle and apoptosis related proteins, such as Bcl-2, Rb, P16, caspase-3, cyclin A and cyclin E, was altered in As(2)O(3) treated NB4 cells. Cell cycle was arrested at G(1) and G(2)/M phases in both cells. It is concluded that the change of cell cycle regulatory proteins plays an important role in decline of the telomerase activity during the proliferation inhibition and apoptosis of NB4 and Jurkat cells induced by As(2)O(3).
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PMID:[Inhibiting effect of arsenic trioxide on telomerase activity of NB4 and Jurkat cell lines]. 1296 62

Rutinoside (rhamnoglucoside; rhamnose+glucose) addition has been examined extensively in the metabolism of flavonoids, however the effect of rutinoside on apoptosis-inducing activity of flavonoids is still unknown. In the present study, the two pairs of flavonoids of hesperetin (HT) and hesperidin (HD; HT-7-rutinose), and naringenin (NE) and naringin (NE-7-rutinose), were used to study their apoptosis-inducing activities in HL-60 cells. Both HD and NI are flavonoids which contain a rutinoside at the C7 of HT and NE, respectively. Results of the MTT assay showed that HT and NE, but not HD and NI, exhibited significant cytotoxic effect in HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells by flow cytometry analysis. HT and NE, but not HD and NI, caused rapid and transient induction of caspase-3/CPP32 activity, but not caspase-1 activity, according to the cleavage of caspase-3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase-3 fragments detected in HT- or NE-, but not in HD- or NI-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in HT- and NE-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bag remained unchanged. The caspase-3 inhibitor, Ac-DEVD-FMK, but not the caspase-1 inhibitor, Ac-YVAD-FMK, attenuated HT- and NE-induced cell death. Interestingly, neither HT nor NE induced apoptosis in the mature monocytic cell line THP-1 and primary human polymorphonuclear cells, as characterized by a lack of DNA ladders, caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and Mcl-1 decrease, compared with those in HL-60 cells. In addition, the rutinoside group in HD and NI was removed by hesperidinase and naringinase, accompanied by the production of HT and NE, respectively, according to HPLC analysis. Accordingly, hesperidinase and naringinase digestion recovered the apoptosis-inducing activity of HD and NI in HL-60 cells. Our experiments provide the first evidence to suggest that rutinoside in flavonoids prevents the induction of apoptosis, and that activation of the traditional caspase-3 cascade participates in HT- and NE-induced apoptosis.
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PMID:Rutinoside at C7 attenuates the apoptosis-inducing activity of flavonoids. 1450 93

Recent researches indicate that ubiquitin-protea some pathway plays an important role in apoptosis regulation. Proteasome inhibitors induce apoptosis in many kinds of neoplastic cells, thus provide a great opportunity for exploring synergy of proteasome inhibitors and other apoptosis-inducing agents. In this study, the effect of the proteasome inhibitor Z-LLL-CHO combined with etoposide (VP16) on leukemic cell lines M-07e and TF-1 was investigated by MTT assay, trypan blue exclusion, flow cytometry and Western blot. The results showed that the combination of Z-LLL-CHO and VP16 was much more effective than either agents alone in promoting cytotoxicity in both cell lines evaluated. Accumulation of cells in S + G2/M phase of the cell cycle was observed in the cells treated with VP16 and Z-LLL-CHO alone, while apparent increase of sub-G0/G1 fraction was detected in cells treated with combination of the agents. The cleavage of Bcl-2 into a shortened 22 kD fragment was detected in M-07e cells exposed to either agents alone, and the fraction of 22 kD fragment was increased in the cells treated with combination of the agents. In conclusion, the combination of Z-LLL-CHO and VP16 enhanced their individual cytotoxic effect by inducing apoptosis, in which increase of S + G2/M fraction in cell cycle as well as the enhanced cleavage of Bcl-2 are the possible mechanism of the additive effect on leukemic cells by Z-LLL-CHO and VP16.
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PMID:[Enhanced apoptosis-inducing effect of etoposide on leukemic cell lines M-07e and TF-1 by the proteasome inhibitor Z-LLL-CHO]. 1457 42

It has been recently established that low-frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high-frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low- and high-frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high-frequency EMFs could affect in vitro cell survival, we cultured acute T-lymphoblastoid leukemia cells (CCRF-CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high-frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro-apoptotic and pro-survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2-12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53-dependent and -independent apoptotic pathways while longer continuous exposure (24-48 h) determined silencing of pro-apoptotic signals and activation of genes involved in both intracellular (Bcl-2) and extracellular (Ras and Akt1) pro-survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self-defense response triggered by DNA damage, could confer to the survivor CCRF-CEM cells a further advantage to survive and proliferate.
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PMID:Exposure to 900 MHz electromagnetic field induces an unbalance between pro-apoptotic and pro-survival signals in T-lymphoblastoid leukemia CCRF-CEM cells. 1460 34

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 micromol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 micromol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.
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PMID:Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro. 1461 77

RIN cells were infected with recombinant Semliki Forest virus (SFV) particles containing the LacZ gene. X-gal staining showed 100% infectivity of the cell cultures and high-level expression of bacterial beta-galactosidase in these cells. The cytopathogenic effects of the SFV infection were studied by measuring the viability of the RIN cells. Comparisons between control RIN cells and Bcl-2 overexpressing RIN cells were done 72 h post-infection. Significant differences in viability levels were observed. The control RIN cells showed in the MTT assay a mean value of 0.156+/-0.017 compared to 0.347+/-0.057 for the RIN/Bcl-2 cells. FACS analysis of cells labelled with propidium iodide indicated that only an average of 4.5+/-0.5% of the control cells were viable 72 h post-infection, while 44.5+/-3.5% of the RIN/Bcl-2 cells were still alive. Thus, the Bcl-2 overexpression clearly protected the SFV-infected cells from undergoing apoptosis.
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PMID:Anti-apoptotic effect of Bcl-2 overexpression in RIN cells infected with Semliki Forest virus. 1464 53

We have demonstrated recently that atypical antipsychotics possess neuroprotective actions in H2O2-mediated and serum-withdrawal models of cell death. In the present study, we compared the ability of atypical and typical antipsychotics to protect against an insult mediated by Abeta(25-35), an apoptogenic fragment of the Alzheimer's disease-related beta-amyloid (Abeta) peptide. Treatment of PC12 cell cultures with Abeta(25-35) did not significantly alter total cellular expression levels of Bax, a proapoptotic Bcl-2 family member, or levels of Bcl-XL, an antiapoptotic analogue. Treatment with Abeta(25-35), however, did result in mitochondrial translocation of Bax, which effectively increased the mitochondrial ratio of Bax to Bcl-X(L). This relative increase in proapoptotic molecules was reduced by pretreatment with atypical (quetiapine and olanzapine) and typical (haloperidol) antipsychotics. We also observed a selective increase in proapoptotic Bcl-XS immunodetection in haloperidol-treated cells, which was evident particularly in the mitochondrial compartment. This increase in proapoptotic molecules may account for the lower neuroprotective potential of haloperidol, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) reduction assay. The disparate neuroprotective effects of atypical and typical antipsychotics/neuroleptics may be due to their respective abilities to regulate pro- and anti-apoptotic protein translocation and expression.
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PMID:Atypical antipsychotics attenuate neurotoxicity of beta-amyloid(25-35) by modulating Bax and Bcl-X(l/s) expression and localization. 1464

Ceramide is a lipid mediator in cell proliferation, differentiation, and apoptosis in many cell lines. However, the molecular mechanisms for ceramide have not been clarified in HC11 mouse mammary epithelial cells. Under phase contrast microscope, C2-ceramide-treated cells clearly showed morphological changes, which were characteristic features of apoptosis. Treatment with C2-ceramide at 10 microM specifically resulted in the death of 50% of the cells after 48 h as assessed by MTT assay. To further investigate which genes contribute to cell death in C2-ceramide-treated cells, we used the reverse transcription-polymerase chain reaction to assess mRNA levels for five genes in the Bcl-2 family and five genes in the caspases family. The steady-state mRNA levels of Bax, Bad and Bak were not significantly changed for 48 h of C2-ceramide treatment. The increases of mRNA levels of Bcl-2 and Bcl-w were observed for the first 3 h of C2-ceramide treatment and the last 24 h between 24 and 48 h. We also found that in HC11 cells, C2-ceramide increased mRNA levels of the caspases family from 6 to 24 h. These results suggest that in the HC11 cells, C2-ceramide promote cell death by mediating the induction of caspases and that HC11 mouse mammary epithelial cells paradoxically up-regulate the expression of Bcl-2 and Bcl-w to prevent C2-ceramide-mediated cell death.
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PMID:C2-ceramide as a cell death inducer in HC11 mouse mammary epithelial cells. 1473 27


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