Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show, in this study, that type I IFN induction of the cyclin-dependent kinase (cdk) inhibitor p21WAF1 in the human Burkitt lymphoma B cell-line Daudi and ensuing cell cycle arrest correlate with the terminal differentiation of these cells, and is ultimately followed by apoptosis and cell death. The expression of p21WAF1 paralleled the onset of G1 arrest and the reduction of surface IgM expression which was used as a marker of the differentiation response, and the IFN treated cells acquired a typical plasma cell-like morphology. The type II IFN IFNgamma, which does not inhibit the growth of Daudi cells, did not induce the expression of p21WAF1, nor affect the expression of surface IgM. The induction of p21WAF1 which paralleled the inhibition of the phosphorylation of the retinoblastoma protein, pRB, was preceded by the strong reduction in c-myc levels. We propose that the coupled down-regulation of c-myc and induction of p21WAF1 may be crucial to the induction of differentiation and G1 arrest in Daudi cells by type I IFN. Growth arrest and differentiation was followed by apoptosis and cell death, and was accompanied by the induction of the activity of the apoptotic ICE-family protease CPP32. G1 arrest and differentiation followed by apoptotic cell death are characteristics of terminal differentiation. Thus, our data suggest that the induction of p21WAF1 and G1 arrest mediated by type I IFN in Daudi cells is part of terminal differentiation response in these cells, highlighting a role for type I IFN as B cell terminal differentiation factors.
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PMID:Type I interferon induction of the Cdk-inhibitor p21WAF1 is accompanied by ordered G1 arrest, differentiation and apoptosis of the Daudi B-cell line. 958 86

HL-60 cells undergo apoptosis when placed at room temperature (RT) [Shimura et al. (1997) FEBS Lett. 417, 379-384]. We report that superoxide anion radical, one of the reactive oxygen species (ROS), was produced after RT treatment. Affinity blot analysis with a biotinylated YVAD-CHO detected the generation of processed peptides with molecular masses of 15-25 kDa. Activation of such an ICE-like protease was completely abolished by N-acetylcysteine and exogenously expressed Bcl-2, known as antioxidants. We concluded that oxidative stress was a critical factor in the signal cascade of the apoptosis. Western blot analysis and experiments using tetrapeptide inhibitors suggested that caspases-1, -3, -4, -6, and -9 did not have an essential role in the apoptotic cascade. It is interesting that cyclosporin A (CsA) blocked RT-induced apoptosis with an inhibition of cytochrome c release from mitochondria. CsA, however, generated a significant amount of ROS with considerable reduction of mitochondrial membrane potential, implying that oxidative stress was one necessary factor for RT-induced apoptosis. It is also likely that mitochondrial membrane potential and the release of apoptotic factors from cytoplasm are differently regulated. Taken together with the reports that some Burkitt lymphoma cells showed apoptosis when exposed at low temperature followed by rewarming, and that hepatocytes or liver endothelial cells are susceptible to cold-induced apoptosis through the ROS function, we propose that studying the mechanism of RT-induced apoptosis of HL-60 cells may provide a therapeutic strategy for pathological conditions involving ROS, such as neurodegenerative diseases and ischemia.
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PMID:Oxidative stress as a necessary factor in room temperature-induced apoptosis of HL-60 cells. 1091 94

We demonstrate here that selective activation of endogenous members of the caspase family and cleavage of substrates responsible for the maintenance of nuclear functional and structural integrity are major effectors of antigen receptor (AgR)- and ionomycin-triggered apoptosis in Ramos-Burkitt lymphoma (Ramos-BL) B cells. Ramos-BL B cells express significant proenzyme levels of caspase-2, -3, -7 and -8, low levels of caspase-6 and are caspase-1-negative. However, while anti-IgM and ionomycin trigger for significant activation of caspase-3, -7 and -8 at 12-16 h and at 4 h post-stimulation respectively, both anti-IgM and ionomycin fail to activate caspase-2 indicating that AgR- and ionomycin-triggered Ramos-BL B cell apoptosis is mediated by the selective activation of, at least, caspase-3, -7 and -8. Anti-IgM triggers for cleavage of the resident nuclear proteins poly(ADP-ribose) polymerase (PARP) at 8 h, lamins B1 and B2 from 12 to 16 h; likewise, ionomycin triggers for degradation of PARP at 2 h, lamins B1 and B2 at 4 h. Signal transduction through CD40 rescues Ramos-BL B cells from AgR- and ionomycin-triggered apoptosis at a very early stage of the apoptotic process by inhibiting both the early cleavage of PARP as well as the activation of caspase-3, -7 and -8 and cleavage of lamin B1; CD40-mediated rescue occurs upstream of CD40-induced expression of Bcl-2 and increased expression of Bcl-xL. In such cellular populations subject to regulation through apoptosis, dysregulation of the apoptotic mechanisms can have devastating consequences by contributing to the pathogenesis of malignancy as well as to lymphoproliferative and autoantibody disorders. An understanding of the role played by caspases in the execution of apoptosis may provide insight into the pathogenesis of these disease states and thereby provide targets for novel therapeutic strategy.
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PMID:Temporal ordering of caspase activation and substrate cleavage during antigen receptor-triggered apoptosis in Ramos-Burkitt lymphoma B cells. 1285 74

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.
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PMID:HIV-related lymphomas in adults served in the public health network: An observational study. 3126 33