Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mouse model of Niemann-Pick disease type C (NPC) carries a genetic defect that causes biochemical changes in lipid levels and a progressive neuropathology that parallels the effects of NPC disease in humans. It is a moot point whether or not the loss of Purkinje and other neuronal cells proceeds by apoptotic death. Therefore, we have introduced into these mice a transgene expressing human Bcl-2 protein which has previously been demonstrated to prevent developmental neuronal death and death induced by a variety of stimuli. The human Bcl-2 transgene was driven by the neuron-specific enolase promoter and was abundantly expressed in Purkinje and other neuronal cells. npc1(-/-)/bcl-2 transgenic mice did not show a significant delay in the onset of neurological disorders. Neuropathological examination of the npc1(-/-)/bcl-2 transgenic mice did not disclose significant differences in numbers of surviving Purkinje cells between the npc1(-/-), tg(+) and npc1(-/-), tg(-) mice. When the npc1(-/-) mice were treated with minocycline, a drug which was shown to inhibit apparent apoptotic death in other mouse models of neurological disease, no delay in onset of neurological disorders were observed in either npc1(-/-), or npc1(-/-) /mdrla(-/-) mice (mdr1a deficiency was used to enhance brain availability of minocycline). Caspase-1 levels were not altered in npc1(-/-) mice, with or without minocycline treatment. These results suggest that Purkinje cell loss in npc1(-/-) mice does not proceed by an apoptotic pathway that can be inhibited by Bcl-2 or minocycline.
...
PMID:Studies on neuronal death in the mouse model of Niemann-Pick C disease. 1211 34

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects 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, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes 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 and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H(2)O(2))-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H(2)O(2)-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.
...
PMID:Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. 1244 60

Francisella tularensis is a facultative intracellular bacterium capable of inducing apoptosis in murine macrophages. Here we analyzed the pathway leading to apoptosis in the murine macrophage-like cell line J774A.1 after infection with F. tularensis strain LVS (named LVS for live vaccine strain). We obtained evidence that the infection affected the mitochondria of the macrophages, since it induced release of the mitochondrial molecule cytochrome c into the cytosol and changed the potential over the mitochondrial membrane. Moreover, activation of caspase 9 and the executioner caspase 3 was also observed in the LVS-infected J774A.1 macrophages. The activated caspase 3 degraded poly(ADP-ribose) polymerase (PARP). All of these events were observed within 9 to 12 h after the initiation of infection, and maximum degradation of a synthetic caspase 3 substrate occurred at 18 h. The internucleosomal fragmentation and PARP degradation resulting from activation of this apoptotic pathway was prevented by the caspase 3 inhibitor Z-DEVD-fmk. No involvement of caspase 1, caspase 8, Bcl-2, or Bid was observed. Thus, the F. tularensis infection induces macrophage apoptosis through a pathway partly resembling the intrinsic apoptotic pathway.
...
PMID:Delineation of the molecular mechanisms of Francisella tularensis-induced apoptosis in murine macrophages. 1287 44

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.
...
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

It has been reported that nipradilol, a nonselective beta- and selective alpha1-receptor antagonist, has cytoprotective effects. We attempted to clarify the effects of nipradilol on the expression of apoptosis associated genes and the activity of nuclear factor-kappaB, a transcription factor, in PC12 cells during serum deprivation induced apoptosis. PC12 cells were cultured in serum free RPMI1640 medium with or without 0.01, 0.1, 1, or 10 microM of nipradilol, or in serum-added medium as a control. The gene expressions of Bax, Bcl-2, Fas, FasL, Caspase-1, 2, 3, and 9, p53, and Smac/DIABLO were examined using a quantitative real time polymerase chain reaction method, while nuclear factor-kappaB activity was examined using an electrophoresis mobility shift assay with a nuclear factor-kappaB consensus sequenced DNA probe. The effects of denitronipradilol were also examined to clarify the effect of nitric oxide donative action. Nipradilol down-regulated Bax gene expression 12 hr after serum deprivation, and that of the capase-9 and Smac/DIABLO genes at 24 hr, compared to the serum-free sample, while it also increased cell viability and decreased DNA ladder formation at 48 hr. However, the expressions of other examined genes were not affected by the agent. In addition, nuclear factor-kappaB activity was increased 2 hr after the addition of 0.1 or 1 microM of nipradilol. In contrast, denitronipradilol did not show any effects toward PC12 cells. Our results suggest that nipradilol may have an effect on apoptosis associated gene expression and nuclear factor-kappaB activity during the prevention of apoptosis via nitric oxide donative action.
...
PMID:Cytoprotection by nipradilol, an anti-glaucomatous agent, via down-regulation of apoptosis related gene expression and activation of NF-kappaB. 1578 Dec 77

Apoptosis regulation has been implicated as a main cause of epithelial dysfunction in patients with ulcerative colitis. Apoptosis can be divided into distinct pathways, which depend on the expression of a large number of apoptosis-related genes. The aim was to elucidate which pathways are dominant in normal and inflamed colonic epithelial cells. An apoptosis-specific gene array expression profiling system of 96 genes was used to determine the expression profile of apoptosis-related genes. Epithelial cells isolated from three patients with active ulcerative colitis were pooled and compared to pooled epithelial cells isolated from three control subjects. Genes found to be three-fold or more overexpressed in ulcerative colitis were subsequently analysed by PCR in a larger population (10 patients with ulcerative colitis, 8 control subjects). Selected genes found not to be regulated were additionally tested by PCR in the same population. Six genes were found to be highly expressed in epithelial cells from both controls and ulcerative colitis patients. These included Bcl-2 antagonist/killer, B lymphoid tyrosine kinase, caspase 14, Harakiri, tumour necrosis factor (TNF) receptor 2, and TNF receptor-associated factor 1 (TRAF1). Three genes were found to be upregulated in ulcerative colitis (p<0.01): caspase 1 and 5, and inhibitor of apoptosis protein 2 (c-IAP2). Both receptor- and mitochondrion-dependent apoptosis pathways are well expressed in enterocytes. Mainly activation-dependent and cytoprotective genes were upregulated in ulcerative colitis.
...
PMID:Expression profiling of apoptosis-related genes in enterocytes isolated from patients with ulcerative colitis. 1690 56

Previously, we found that human histocytic lymphoma U937 cells possessed high susceptibility to oridonin-induced cell death, but the molecular mechanisms in response to oridonin remain unclear. In this study, U937 cells showed susceptible to apoptosis induced by 27 microM oridonin and an agonistic anti-Fas IgM mAb (CH-11) (500 ng/ml) as a Fas-sensitized positive control. Caspase 8 inhibitor z-IETD, but neither caspase 1 inhibitor Ac-YVAD nor caspase 10 inhibitor z-AEVD, effectively blocked oridonin-induced cell death as well as DNA fragmentation. Western blot analysis showed the up-regulated expression of Fas, FasL, and FADD, and down-regulated expression of procaspase 8, suggesting that Fas/FasL pathway was activated in oridonin-induced cell apoptosis. Further, stimulation of U937 cells with oridonin and CH11 resulted in significant ERK MAPK activation. However, inhibition of ERK by PD98059 reversed oridonin-induced cell death as well as the activation of caspase 8, indicating that ERK-mediated control occured upstream of caspase 8. Simultaneously, ERK activation accounted for the release of cytochrome c, but failed to influence decreased Bcl-2 expression induced by oridonin. Taken together, these results suggest that Fas/FasL signaling pathway-mediated ERK activation sensitized U937 cells to mitochondrial pathway-mediated apoptosis induced by oridonin.
...
PMID:Fas/FasL signaling allows extracelluar-signal regulated kinase to regulate cytochrome c release in oridonin-induced apoptotic U937 cells. 1694 1

In the present study, we found that baicalein (BE), but not its glycoside baicalin (BI), induced apoptosis in human leukemia HL-60 and Jurkat cells, but not in primary murine peritoneal macrophages (PMs) or human polymorphonuclear (PMN) cells, by the MTT assay, LDH release assay, and flow cytometric analysis. Activation of the caspase 3, but not caspase 1, enzyme via inducing protein processing was detected in BE-induced apoptosis. The ROS-scavenging activity of BE was identified by the anti-DPPH radical, DCHF-DA, and in vitro plasmid digestion assay, and none of chemical antioxidants including allpurinol (ALL), N-acetyl-cystein (NAC), and diphenylene iodonium (DPI) affected BE-induced apoptosis in HL-60 cells. This suggests that apoptosis induced by BE is independent of the production of ROS in HL-60 cells. Interestingly, the apoptotic events such as DNA ladders formation and activation of the caspase 3 cascade were significantly blocked by TPA addition in the presence of membrane translocation of PKCalpha, and TPA-induced protection was reduced by adding the PKC inhibitors, GF-109203X and staurosporin. TPA addition induces the phosphorylation of JNKs and ERKs, but not p38, protein in HL-60 cells, and incubation of HL-60 cells with JNKs inhibitor SP600125, but not ERKs inhibitor, PD98059 or the p38 inhibitor SB203580, suppressed the protective effect of TPA against BE-induced apoptotic events including DNA ladders, apoptotic bodies, caspase 3 and D4-GDI protein cleavage in according with blocking JNKs protein phosphorylation. In addition, PKC inhibitor GF-109203X treatment blocks TPA-induced ERKs and JNKs protein phosphorylation, which indicates that activation of PKC locates at upstream of MAPKs activation in TPA-treated HL-60 cells. Additionally, a loss in mitochondrial membrane potential with a reduction in Bcl-2 protein expression, the induction of Bad protein phosphorylation, and translocation of cytochrome c from mitochondria to the cytosol were observed in BE-treated HL-60 cells, and these events were prevented by the addition of TPA. GF-109203X and SP600125 suppression of TPA against cytochrome c release induced by BE was identified. This suggests that activation of PKC and JNKs participate in TPA's prevention of BE-induced apoptosis via suppressing mitochondrial dysfunction in HL-60 cells.
...
PMID:12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells. 1701 57

When Chinese hamster ovary (CHO) cells were grown in suspension and deprived of serum, 40% of them became apoptotic after 72 hours, as determined by flow cytometry analysis of TUNEL-labelled cells. Cell viability, assessed by erythrocin B staining, decreased correspondingly. An increase in the total fraction of cells expressing interleukin converting enzyme (ICE; caspase 1), B-cell lymphoma 2 protein (Bcl-2,) and Bcl-2 associated x protein (Bax) was shown by antibody probing and subsequent flow cytometry. The p53 tumour suppressor gene product level remained low within the cell population. Insulin-like growth factor-1 (IGF-1) inhibited cell death in a concentration-dependent manner, and at 20 ng/ml, cell viability was maintained close to 100% and no apoptotic cells were detected. Also, insulin was shown to inhibit cell death - at 1.0 microg/ml, cell viability was 95%, whereas 10% of the cells stained for apoptosis. At the highest concentrations of IGF-1 and insulin, the expression of ICE, Bcl-2 and Bax was fully suppressed, whereas the p53 product level increased, despite still being detectable in a minority of cells. Under these conditions, IGF-1 may increase p53 expression to restrain abnormal cell proliferation. It is concluded that special attention should be paid to exposure and culture conditions that induce acquired susceptibility to a toxic insult, during the development and validation of cell-based assays.
...
PMID:Insulin and IGF-1 mediated inhibition of apoptosis in CHO cells grown in suspension in a protein-free medium. 1765 Sep 54

BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-x(L) and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-x(L) and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-x(L) and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-x(L) proteins without N-terminal 61 residues, His(6)-NDelta61-Bcl-x(L)-CDelta21 and NDelta61-Bcl-x(L)-CDelta21, form oligomers in solution, whereas Bcl-x(L)-CDelta21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of alpha-helices upon deletion of N-terminal residues. NDelta61-Bcl-x(L)-CDelta21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.
...
PMID:Oligomerization of BH4-truncated Bcl-x(L) in solution. 1769 89


<< Previous 1 2 3 4 5 Next >>

---