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

Lipoproteins of Mycoplasma salivarium and Mycoplasma fermentans preferentially induced necrotic cell death in lymphocytic cell lines, MOLT-4 and Raji, and in one monocytic cell line, THP-1, whereas they preferentially induced apoptotic cell death in another monocytic cell line, HL-60. These findings were also supported by ultrastructural observations by the use of scanning and transmission electron microscopes and by agarose gel electrophoresis of the genomic DNA. The lipoproteins activated caspase-3 in both MOLT-4 and HL-60 cells, which was assessed by the cleavage of the synthetic substrate DEVD-pNA and the endogenous substrate poly(ADP-ribose) polymerase. The cytotoxicity to MOLT-4 and HL-60 cells was inhibited by various caspase inhibitors, Ac-DMQD-CHO, Ac-IETD-CHO, and Z-VAD-FMK. The cytotoxicity was also partially suppressed by the monoclonal antibody to Toll-like receptor 2. Thus this study demonstrated that mycoplasmal lipoproteins induce caspases-dependent necrotic and apoptotic cell death in lymphocytes and monocytes/macrophages, which is partially induced by TLR2-mediated signaling.
 ...
PMID:Mycoplasmal lipoproteins induce toll-like receptor 2- and caspases-mediated cell death in lymphocytes and monocytes. 1206 29

We have previously reported that in a MOLT-4 leukemia cell line the acquired resistance to 9-beta-D-arabinofuranosylguanine (Ara-G) is due to deficiency of the activating enzymes deoxyguanosine kinase and deoxycytidine kinase [Biochem. Biophys. Res. Commun. 293 (5) (2002) 1489]. In this study we investigated whether apoptotic pathways are affected in two human T-cell lymphoblastic MOLT-4 cell lines with acquired resistance to Ara-G. In contrast to the MOLT-4 wild type cells, Ara-G resistant cells displayed no increase in caspase-3 or caspase-9 activity, DNA fragmentation, cytochrome c release or a drop in the mitochondrial membrane potential (DeltaPsi(mito)) upon Ara-G treatment. A drop in the DeltaPsi(mito) was induced in wild type cells after treatment with tributyltin, an inducer of mitochondrial permeability transition, and with carbonyl cyanide m-chlorophenylhydrazone, an uncoupling agent that reduces the DeltaPsi(mito), although not in Ara-G resistant cells. Ara-G resistant cells displayed higher levels of the anti-apoptotic protein Bcl-xL in immunoblots. A recent study indicates that Ara-G-induced apoptosis is mediated in part via the Fas pathway [Cancer Res. 43 (2047) (2002) 411]. When cells were treated with anti-Fas antibody, the wild type cell line exhibited increased caspase-3-like activity but the Ara-G resistant cells did not. Using FACS analysis and semi-quantitative PCR, 3-6-fold decreased protein levels and almost no detectable mRNA levels of Fas in the resistant cells were recorded. These data indicate that the inability to induce apoptosis via both the apoptosome pathway and the Fas pathway, due to increased levels of Bcl-xL and a lack of Fas, contributes to Ara-G resistance. This resistance to apoptosis in Ara-G resistant cells may serve to explain the overall resistance to a variety of anti-neoplastic drugs.
 ...
PMID:Resistance to mitochondrial- and Fas-mediated apoptosis in human leukemic cells with acquired resistance to 9-beta-D-arabinofuranosylguanosine. 1241 45

It has been demonstrated that caspase-3 is responsible for determining the mode of cell death, i.e., apoptosis or necrosis. To characterize the mode of cell death induced by the inhibition of caspase-3, we have studied the effects of Ac-DEVD-CHO, Ac-YVAD-CHO, and Ac-IETD-CHO, inhibitors of caspases, on structural changes in X-irradiated human leukemic MOLT-4 cells. When cells were irradiated with X-rays and incubated in the presence of Ac-DEVD-CHO, the expression of cell death, as measured by the dye exclusion test, was inhibited, whereas no such change was observed in colony-forming ability. The hallmarks of apoptosis, i.e., nuclear condensation and DNA ladder formation, were depressed. However, a new type of nuclear morphology appeared. The sum of the frequencies of apoptosis and this new type of nuclear structure corresponded to the frequency of X-ray-induced apoptosis for cells incubated in the absence of Ac-DEVD-CHO. Removal of Ac-DEVD-CHO during the course of post-irradiation incubation increased apoptotic nuclear condensation accompanied by a slight decrease in the frequency of the new type of nuclear structure. When Ac-IETD-CHO was used in place of Ac-DEVD-CHO, inhibition of cell death (apoptosis) was also observed, but not in the case of Ac-YVAD-CHO. These results suggest that the inhibition of caspase-3 diminishes the expression of apoptotic hallmarks with no effect on cell survival, that the morphology observed in the presence of Ac-DEVD-CHO is an apoptosis-related structure, and that the cell death observed is a programmed cell death independent of caspase-3. The development of this mode of cell death was slower than that of apoptosis by 4 h.
 ...
PMID:Time sequence analysis of caspase-3-independent programmed cell death and apoptosis in X-irradiated human leukemic MOLT-4 cells. 1245 29

The cytotoxicities of lipoproteins of Mycoplasma fermentans and Mycoplasma salivarium to a lymphocytic cell line, MOLT-4, and a monocytic cell line, HL-60, was upregulated by ATP added extracellularly in a dose-dependent manner. These lipoproteins induced ATP release and plasma membrane permeability increase in these cell lines. In addition, periodate-oxidized ATP, an antagonist for P2X purinergic receptors, suppressed the cytotoxicity of the lipoproteins, suggesting the possibility that P2X receptors for ATP play crucial roles in the cytotoxicity. Activation of caspase-3 induced by the lipoproteins, which was assessed by the cleavage of the synthetic substrate DEVD-pNA and the endogenous substrate poly(ADP-ribose) polymerase, was also upregulated and downregulated by extracellular ATP and periodate-oxidized ATP, respectively. On the basis of these results, this study suggests that mycoplasmal lipoproteins induce the permeability increase in lymphocytes and monocytes, by which ATP is released, and the ATP regulates the cytotoxicities of the lipoproteins to the cells, possibly by interaction with ATP receptors such as P2X purinergic receptors.
 ...
PMID:Extracellular ATP regulates cell death of lymphocytes and monocytes induced by membrane-bound lipoproteins of Mycoplasma fermentans and Mycoplasma salivarium. 1247 45

In recent years, it has been reported that bisphosphonates inhibited the cell cycle of myeloma cells to inhibit cell proliferation directly, and it was also reported that bisphosphonates induced apoptosis of myeloma cells in vitro. Recently, YM529 was developed as a new third-generation bisphosphonate. In our experiment, we investigated whether YM529 showed an antitumor effect on hematopoietic tumor cell lines other than myeloma, and we compared YM529 with YM175, which had a relatively more potent antitumor effect than that of existing bisphosphonates. We found that YM529 inhibited cell proliferation in various hematopoietic tumor cell lines (acute promyelocytic leukemia cell line HL-60, chronic myeloid leukemia cell line K562, histiocytic lymphoma cell line U937, lymphoblastic leukemia T cell line Jurkat, acute lymphoblastic leukemia T cell line MOLT-4, lymphoblastic leukemia B cell line CCRF-SB) including myeloma (myeloma cell line HS-Sultan) dose-dependently and time-dependently to a degree equivalent or superior to that in myeloma, and induced apoptosis at a lower concentration as compared with YM175. We confirmed many dead cells as well as apoptosis based on the detection of the nuclei with separate globular structure, the activation of caspase-3, and the decrease in mitochondrial transmembrane potential. Therefore, it is concluded that further utilization of YM529 can be expected against hematopoietic tumor cells in the future.
 ...
PMID:Apoptosis-inducing effect of a new bisphosphonate, YM529, on various hematopoietic tumor cell lines. 1252 Jan 82

We have established that CpG oligodeoxynucleotide 5mers, of sequence type CGNNN (N = A, G, C or T), rapidly induce apoptosis/cell cycle arrest in human leukaemia lines. The 5'-CpG is obligatory for these effects. Induction of apoptosis in MOLT-4 cells did not require new protein synthesis and was insensitive to the caspase 3 inhibitor, Ac-DEVD-CHO, although the latter abrogated DNA laddering, phosphatidylserine externalization and collapse of the mitochondrial transmembrane potential. A subline of MOLT-4 cells, MOLT-4CpGR, was selected for acquired resistance to CpG 5mers. Differences in gene expression between MOLT-4 and MOLT-4CpGR cells were identified following three independent reciprocal cDNA subtractions, consensus selection and virtual cloning through targeted display. Several known genes were implicated in the action of or resistance to CpG oligodeoxynucleotide 5mers. Their protein products listed below immediately suggest cell signalling pathways/processes worthy of further investigation in elucidating the mechanism of CpG 5mer activity: caspase 2, the transcription factors Atf4, Hic, HoxB3 and Rqcd1, the splicing factors Rbmx, Sfrs5 and Sfrs7, the DNA replication factors Mcm5 and Brd4, phosphoinositide-3-kinase, annexin A1, mucosa-associated lymphoid tissue lymphoma translocation 1 and three enzymes involved in protein ubiquitylation, Siah1, Gsa7 and Nin283.
 ...
PMID:CpG oligodeoxynucleotide 5mer-induced apoptosis in MOLT-4 leukaemia cells does not require caspase 3 or new protein synthesis. 1271 74

The c-Jun N-terminal kinases (JNKs) are a subfamily of the mitogen-activated protein kinases (MAPKs). The JNKs are encoded by three separate genes (jnk1, jnk2, and jnk3), which are spliced alternatively to create 10 JNK isoforms that are either p46 or p54 in size. In this study, we found that the p52 form of JNK emerged in human leukemia MOLT-4 or U937 cells following X-irradiation or heat treatment. The accumulation of p52 coincided with the reduction of p54 JNK. On the other hand, the amounts of p46 JNK did not change by X-irradiation. Induction of the p52 form of JNK also paralleled the appearance of the active form of caspase-3 and was suppressed by a caspase-specific inhibitor, Ac-DEVD-CHO, but not by Ac-YVAD-CHO. In vitro cleavage assays indicated that recombinant human JNK1beta2 and JNK2beta2 were cleaved by caspase-3, and that the mutation of aspartic acid at position 413 of JNK1beta2 or 410 of JNK2beta2 to alanine abolished the cleavage. Altogether, our results demonstrated that p54 JNKs, at least JNK1beta2 and JNK2beta2, were new selective targets of caspases in JNK splicing variants, and suggested that the p52 form could serve as a marker of apoptosis.
 ...
PMID:Caspase-mediated cleavage of JNK during stress-induced apoptosis. 1282 Nov 18

Little information is available regarding possible synergistic or antagonistic biochemical interactions among polyphenols contained in fruits and vegetables. Identifying potential interactions among these compounds may help to define the efficiency of polyphenol-containing foods in cancer prevention as related to structure-function activity of the compounds. The objective of this study was to investigate interactions between quercetin and ellagic acid, two polyphenolics that are present predominantly in small fruits, on cell death and proliferation-related variables in the MOLT-4 human leukemia cell line. Assays were performed to determine cell cycle kinetics, proliferation, apoptotic DNA-fragmentation and caspase-3-activity after 12, 24 and 48 h. Ellagic acid significantly potentiated the effects of quercetin (at 5 and 10 micro mol/L each) in the reduction of proliferation and viability and the induction of apoptosis. Significant alterations in cell cycle kinetics were also observed. The synergy was confirmed by an isobolographic analysis of the cell proliferation data. The interaction of ellagic acid and quercetin demonstrated an enhanced anticarcinogenic potential of polyphenol combinations, which was not based solely on the additive effect of individual compounds, but rather on synergistic biochemical interactions.
 ...
PMID:Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells. 1288 56

A post-irradiation treatment of the human leukemia cell line MOLT-4 with the antioxidant Trolox attenuated caspase-3 dependent apoptosis. The increase in the p53 expression and SAPK/JNK activation after X irradiation was also inhibited by a Trolox treatment, but the expression of BCL-2 and BAX, which would occur downstream from p53, was not changed. Studies on the effects of the intracellular calcium chelator BAPTA-AM on the induction of apoptosis and the activation of SAPK/JNK and caspase-3 proved that the chelation of calcium merely delayed the onset of radiation-induced apoptosis and the activation of SAPK/JNK and caspase-3. When the effects of the protein synthesis inhibitor cycloheximde on the apoptotic signaling pathways, including the activation of caspase family proteins and SAPK/JNK, were investigated, the expression of death receptor Fas through SAPK/JNK activation was found to be required for radiation-induced apoptosis. Finally, the relationship between the amounts of DNA dsb and induction of apoptosis was examined by irradiating BrdU-incorporated cells. An increase in DNA dsb caused by BrdU was found, but the induction of apoptosis was not enhanced. From these data, we could get no positive evidence for DNA as a target of X-rays and p53 as an indispensable factor to induced apoptosis in X-irradiated MOLT-4 cells.
 ...
PMID:Induction of apoptosis through the activation of SAPK/JNK followed by the expression of death receptor Fas in X-irradiated cells. 1464 22

Galectin (Gal)-3, a M(r) 31000 member of the beta-galactoside-binding protein family, is a multifunctional protein implicated in a variety of biological functions, including tumor cell adhesion, proliferation, differentiation, angiogenesis, apoptosis, cancer progression, and metastasis. Here, we report that secreted extracellular Gal-3 can signal apoptosis of human T leukemia cell lines, human peripheral blood mononuclear cells, and activated mouse T cells after binding to cell surface glycoconjugate receptors through carbohydrate-dependent interactions because the apoptotic effect was found to be inhibited by lactose, specific sugar inhibitor, and to be dose dependent. However, the apoptosis sensitivity to Gal-3 varied among the different cell lines tested. We report that Gal-3-null Jurkat, CEM, and MOLT-4 cells were significantly more sensitive to exogenous Gal-3 than SKW6.4 and H9 cells, which express Gal-3, suggesting a cross-talk between the antiapoptotic activity of intracellular Gal-3 and proapoptotic activity of extracellular Gal-3. Furthermore, Gal-3-transfected CEM cells were found to be more resistant to C(2)-ceramide-induced apoptosis than the control CEM cells. Identification of Gal-3 cell surface receptors revealed that Gal-3 binding to CD7 and CD29 (beta(1) integrin) induced apoptosis. Gal-3 binding to its cell surface receptors results in activation of mitochondrial apoptosis events including cytochrome c release and caspase-3 activation, but not caspase-8 activation. Taken together, these results suggest that the induction of T-cell apoptosis by secreted Gal-3 may play a role in the immune escape mechanism during tumor progression through the induction of apoptosis to cancer-infiltrating T cells. The induction of T-cell apoptosis by secreted Gal-3 is dependent in part on the presence or absence of cytoplasmic Gal-3, providing a new insight for the immune escape mechanism of cancer cells.
 ...
PMID:CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. 1467 89


<< Previous 1 2 3 4 5 6 Next >>