Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas and p55 tumor necrosis factor receptor (TNFR) transfer an apoptosis signal when they are crosstinked with their ligands or agonistic antibodies. However, the signal transduction mechanism of apoptosis via Fas and p55 TNFR has not yet been elucidated. We previously described a recessive mutant UK110 from the human monocytic leukemia U937 cell line, that showed resistance against Fas- and p55 TNFR-mediated apoptosis. By cytogenetic analysis and microcell-fusion method, we demonstrate here that introduction of chromosome 22 can specifically restore the sensitivity to Fas- and TNF-mediated apoptosis in UK110 cells. Moreover, introduction of chromosome 22 into UK110 can complement the processing of interleukin-1 beta converting enzyme (ICE)-like proteases, such as CPP32/Yama/Apopain and ICH-1L, after treatment with anti-Fas and anti-p55 TNFR antibodies. These results suggest that the product of a gene located on chromosome 22 participates in the Fas-and p55 TNFR-mediated apoptosis at a point upstream of ICE-like proteases.
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PMID:Chromosome 22 complements apoptosis in Fas-and TNF-resistant mutant UK110 cells. 870 May 52

It has been well documented that caspase-1 (interleukin-1beta-converting enzyme, ICE) and its related cysteine proteinases such as caspase-3 (CPP32, apopain) and caspase-2 (ICH-1L) play important roles in apoptosis. In the present study, these genes were inserted into an inducible eukaryotic expression vector, pMSG, and transfected into NIH 3T3 mouse fibroblasts. The expression of caspases-1 and -3 was effectively induced by treatment with dexamethasone (Dex). The expression of caspase-2 was elevated in the transfected cells without treatment with Dex but was not further stimulated by Dex. High expression of these proteases alone induced neither apoptosis-like cell death nor any morphological change. However, the expression of caspase-1 but not of caspase-2 or -3 enhanced chemosensitivity toward cytotoxic anticancer drugs such as aclarubicin, epirubicin, adriamycin, nimustine and ifosfamide. It is thus concluded that caspase-1 mediates cytotoxic effects of these drugs.
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PMID:Enhancement of chemosensitivity toward anticancer drugs by high expression of caspase-1 in NIH 3T3 cells. 949 96

Caspases are aspartate-specific cysteine proteases that play a pivotal role in drug-induced cell death. We designed RT-PCR assays to analyse the expression of CASP-3, CASP-4, CASP-6 and the long and short isoforms of CASP-2 genes in human cells. These genes heterogeneously coexpress in leukemic cell lines and bone marrow samples from patients with de novo acute myelogenous leukemia at diagnosis. Treatment of U937 and HL60 leukemic cells and HT29 colon carcinoma cells with the topoisomerase II inhibitor etoposide upregulates CASP-2 and CASP-3 genes in these cells before inducing their apoptosis. This effect of etoposide is not observed in K562 cells and bcl-2-transfected U937 cells which are less sensitive to drug-induced apoptosis. Nuclear run-on experiments demonstrate that etoposide increases CASP gene transcription in U937 cells, an effect that is prevented by Bcl-2 overexpression. Upregulation of CASP genes is associated with an enhanced synthesis of related procaspases that precedes the appearance of apoptosis markers including caspase-3 activation, poly(ADP-ribose) polymerase cleavage and internucleosomal DNA fragmentation. These results suggest that the ability of tumor cells to upregulate CASP-2 and CASP-3 genes in response to cytotoxic drugs could be predictive of their sensitivity to drug-induced apoptosis.
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PMID:Upregulation of CASP genes in human tumor cells undergoing etoposide-induced apoptosis. 967 9

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.
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PMID:Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells. 971 43

Continuous and long-lasting exposure to tert-butylhydroperoxide (t-BOOH) increased the number of apoptotic SH-SY5Y human neuroblastoma cells both in the presence and in the absence of the intracellular Ca(2+) ion chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). In addition, t-BOOH exposure induced activation of CPP32, as demonstrated by poly-(ADP-ribose) polymerase (PARP) cleavage, and of ICH-1L caspases. Exposure to t-BOOH also induced a time-dependent release of cytochrome c. Interestingly, in the presence of BAPTA, CPP32 activation still occurred, whereas ICH-1L activation was blocked. Ac-DEVD-CHO, an inhibitor of CPP32 activity, prevented the appearance of apoptotic cells, whereas the inhibitor of ICH-1L activity Z-VDVAD-FMK did not. Collectively, these findings demonstrate that in SH-SY5Y neuroblastoma cells exposure to continuous and long-lasting oxidative stress induced activation of caspase-3 that was independent of intracellular Ca(2+) ion concentration ([Ca(2+)](i)) elevation but led to cell apoptosis. In contrast, caspase-2 activation was dependent on [Ca(2+)](i) increase but did not result in apoptosis.
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PMID:Ca(2+)-independent caspase-3 but not Ca(2+)-dependent caspase-2 activation induced by oxidative stress leads to SH-SY5Y human neuroblastoma cell apoptosis. 1199 72