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)

Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-beta signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-beta or, to a lesser extent, by other apoptotic agents. Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs. Mutation of the P-loop of ARTS abrogates its competence to activate caspase 3 and to induce apoptosis. Taken together, these observations expand the functional attributes of septins previously described as having roles in cytokinesis and cellular morphogenesis.
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PMID:A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. 1114 68

The second mitochondria-derived activator of caspase, Smac, is an apoptosis-related protein. Smac releases inhibition of the IAP family from caspase-3 to induce apoptosis. Smac is expressed in some malignant tumor cells and is released from mitochondria into the cytosol after death receptor stimulation to promote apoptosis of tumor cells. In this study, we found down-regulated Smac protein expression in hepatocellular carcinoma (HCC) tissues, compared to that in non-tumor hepatic tissues. Simultaneously, caspase-3 expression also decreased in HCC tissues. HCC cell lines did not undergo apoptosis after TRAIL stimulation, although Smac was expressed in these HCC cells. Ectopic Smac alone did not induce cell death, but could sensitize HCC cells to TRAIL stimulation. With over-expression of Smac in HCC cells, TRAIL induced by 10% HCC cell death. The role of Smac in apoptosis signaling pathway in HCC cells warrants further study.
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PMID:Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma. 1279 4

Oxalate is not only considered to be one of the main constituents of urinary stones, but it also has toxic effects on renal tubular epithelial cells, affecting the pathogenesis of nephrolithiasis. We tried to elucidate the effects of oxalate on human renal tubular epithelial cells (HK-2 cells). In addition, we investigated whether the toxic effect of oxalate occurs by apoptosis, and determined the expression of Bcl-2 family and caspase 9 proteins known as apoptosis-related protein. HK-2 cells were incubated with different concentrations of oxalate, and the effect of oxalate on the growth of the cells was assessed by MTT assay. A caspase-3 activity assay and TUNEL assay were performed on HK-2 cells after oxalate exposure in order to evaluate apoptosis. Immunoblot analysis of Bax, Bcl-2, Bcl-xL, and caspase-9 were performed. Oxalate exposure resulted in significant growth inhibition of HK-2 cells as oxalate concentrations increased. The toxic effect of oxalate on HK-2 cells was considered to occur through apoptosis, as suggested by the increase of caspase-3 activity. The percentage of positive nuclei stained using the TUNEL method was 18+/-2.3 in oxalate-treated cells and 2.5+/-0.9 in untreated cells (P<0.05). Bax and caspase-9 protein expression increased significantly as oxalate concentrations increased, but Bcl-2 protein expression decreased. There was no difference in Bcl-xL protein expression among the various concentrations of oxalate. Our results show that oxalate has a toxic effect on HK-2 cells and that this effect is induced by apoptosis, which may be mediated by an intrinsic pathway.
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PMID:Apoptosis induced by oxalate in human renal tubular epithelial HK-2 cells. 1575 46

Occupational exposure and experimental intoxication with n-hexane or its metabolite 2,5-hexanedione (HD) produce a central-peripheral neuropathy. However, the mechanism remains unknown. We hypothesized that HD affected the expression of Bcl-2, Bax and Caspase-3 in the central nervous system (CNS) and the peripheral nervous system (PNS). Male adult Wistar rats were administered by intraperitoneal injection at a dosage of 200 or 400 mg/kg HD, five days per week for 8 weeks. Samples of the cerebral cortex, cerebellum, spinal cord and sciatic nerves were collected and examined for Bcl-2, Bax and Caspase-3 expression using Western blotting. Subchronic exposure to HD resulted in significantly increased expression of both anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax and Caspase-3 in cerebral cortex and cerebellum, which exhibited a dose-dependent pattern. Though little change was detected in spinal cord, our results showed that the expression of Bcl-2, Bax and Caspase-3 was markedly enhanced in the sciatic nerves. These findings suggested that the changes of apoptosis-related protein level in rat nerve tissues were associated with the intoxication of HD, which might be involved in early molecular regulatory mechanism of apoptosis in the HD-induced neuropathy.
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PMID:Expression of Bcl-2, Bax and Caspase-3 in nerve tissues of rats chronically exposed to 2,5-hexanedione. 1749 5

Nonylphenol (NP) is an endocrine disruptor, which has been reported to have adverse effects on reproductive and immune systems. However, the influence of NP on the central nervous system (CNS) has not been extensively explored. The present study was performed to investigate the effects of chronic administration of NP on the apoptosis-related protein expression in mouse brain by in situ hybridization, RT-PCR and immunoblotting assays. The expression of bcl-2 mRNA was down-regulated by NP at the doses of 100 and 200mg/(kg day) (p<0.05), whereas the expression of bax mRNA was not affected in NP treated mice (p>0.05). Furthermore, as the main executor of apoptosis, the expression of active caspase-3 was up-regulated by 100 and 200mg/(kg day) NP (p<0.01), which is in accord with the results of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) (p<0.05). These results suggest that chronic application of NP could sensitize the mice brain to apoptosis.
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PMID:Chronic application of nonylphenol-induced apoptosis via suppression of bcl-2 transcription and up-regulation of active caspase-3 in mouse brain. 1851 16

The present study examined the anti-proliferative effects of piplartine on the human prostate cancer cell line PC-3. This is the first report demonstrating the piplartine anti-cancer activity toward prostate cancer cell lines, although its precise mechanism of action is still not completely defined. In MTT assays, it preferentially inhibited growth of androgen-independent PC-3 cells in a dose-dependent (3-30 microM) and time-dependent (12-48 h) manner. In PC-3 cells, it showed an IC50 of 15 microM after 24 h of treatment. After a 24-30 microM treatment for 24 h, there were some reduction of cell volume, cell vacuolization, chromatin condensation and increased number of apoptotic cells visible by light and fluorescence microscopy. Agarose gel electrophoresis revealed that cells treated with piplartine exhibited DNA fragmentation. In addition, growth inhibition of PC-3 cells was associated with G2/M arrest and sub-G1 accumulation. Higher concentrations (24-30 microM) of piplartine modulated apoptosis-related protein expression by down-regulating cdc-2 expression and up-regulating PARP/procaspase-3 cleavage. Also, PC-3 cells treated with piplartine demonstrated caspase-3 activation, as observed with an in vitro caspase-3 colorimetric assay kit. Taken together, these results demonstrated that high concentrations of piplartine exhibited anti-proliferative and anti-cancer effects on PC-3 cells and that caspase-3-mediated PARP cleavage and cell cycle arrest at G2/M phase are involved in the underlying cellular mechanism of the apoptosis process.
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PMID:Piplartine induces caspase-mediated apoptosis in PC-3 human prostate cancer cells. 1881 19

1. It has been shown that inhaled isoflurane limits the size of myocardial infarcts. The aim of the present study was to examine the effects of emulsified isoflurane on cardiac function and myocardial apoptosis in an ischaemia model of myocardial injury. 2. In the first study, 48 rats were randomly allocated to six groups (n = 8 in each): control (saline); emulsified isoflurane (EIso) at 1, 2 or 4 mL/kg; 30% intralipid (vehicle for EIso); and sham operated. Rats received isovolumetric intravenous infusions for 30 min and then, 30 min after cessation of the infusion, 90 min coronary occlusion. Haemodynamics and myocardial infarct size were measured. In the second study, another 48 rats were randomized into six groups (n = 8 in each). After 90 min ischaemia, rats were killed for histopathological study, immunohistochemical evaluation and apoptosis measurement. 3. Pretreatment with 2 and 4 mL/kg EIso significantly attenuated decreases in left ventricular systolic pressure and dP/dt(max), and increases in left ventricular end-diastolic pressure and -dP/dp(max), and alleviated myocardial injury compared with the control, intralipid and 1 mL/kg EIso groups (P < 0.05). Infusion of 1 mL/kg EIso and intralipid had no effect on haemodynamics, infarct size or histological variables. 4. Expression of Bcl-2 was increased, whereas expression of Bax and caspase 3 was decreased, after preconditioning with 2 and 4 mL/kg EIso (P < 0.05). The apoptotic index in the 2 and 4 mL/kg Eiso-treated groups was reduced compared with that in the control and intralipid groups (P < 0.01). 5. In conclusion, EIso ameliorates cardiac dysfunction, attenuates myocardial damage and inhibits apoptosis after ischaemia, which may be attributed, in part, to diminished expression of apoptosis-related protein.
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PMID:Effects of emulsified isoflurane on haemodynamics and cardiomyocyte apoptosis in rats with myocardial ischaemia. 1920 25

The aim of study was to investigate the effect of a traditional Chinese medicine, emodin, on proliferation and apoptosis in T lymphocytic leukemic cell line Jurkat and its mechanisms. Cell proliferation inhibition was detected by MTT assay. Cell apoptosis was measured by DNA ladder and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The expressions of related proteins and caspase family members were determined by Western blot. The results showed that emodin inhibited proliferation in Jurkat cells, with an IC50 about 20 micromol/L and induced cell apoptosis in both time-and dose-dependent manners. The expressions of proliferation-related protein C-MYC, hTERT and apoptosis-related protein BCL-2 were down-regulated in a time dependent manner after the treatment with emodin. The expressions of procaspase-3, -8 and -9 all decreased while activated caspase-3 and PARP expressions were up-regulated. It is concluded that emodin can remarkably inhibit cell proliferation and induce apoptosis in Jurkat cells. The down-regulation of proliferation-related proteins C-MYC, hTERT and apoptosis-related protein BCL-2 expressions and activation of caspase cascade may be involved in the process of apoptosis.
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PMID:[Effect of emodin on induction of apoptosis in jurkat cells and its possible mechanisms]. 1984 Apr 50

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), a natural anthraquinone derivative isolated from Rheum palmatum L, has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. Our preliminary study showed that emodin had highly cytotoxic effect on human chronic myeloid leukemia K562 cell lines. This study was performed to investigate the anti-tumor effect of emodin in human K562 cell line in vitro and in vivo. The MTT data showed the inhibition on growth of K562 cells following emodin treatment. Flow cytometry showed that the cell cycle of K562 cells was arrested in G(0)/G(1) phase. Through Western blot analysis, we found that the apoptosis-related protein Bcl-2 was decreased in a dose-dependent manner and the Bax was increased after emodin treatment. Moreover, activations of caspase-3, -8 and -9 were demonstrated in vitro and in vivo. The increased Bax concurrent with the decreased of Bcl-2 indicated that emodin treatment might result in apoptosis of K562 cells. The cell apoptosis was also directly demonstrated by Annexin V-FITC, and DNA fragmentation assay. Additionally, the tumoricidal effect of emodin was measured using a xenograft nude mice model. We found that, after inoculated with the K562 cells, the nude mice treated with emodin showed a significant decrease of tumor volume and tumor weight in comparison to the control. Emodin could cause the regression of tumor. Both in vitro and in vivo studies suggest that emodin can be developed as a promising anti-chronic myeloid leukemia drug.
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PMID:Anti-tumor activity of emodin against human chronic myelocytic leukemia K562 cell lines in vitro and in vivo. 1985 84

This study was aimed to investigate the apoptosis effect of gossypol acetic acid on classic human multiple myeloma RPMI8226 cell line in vitro and its mechanism. The inhibitory effect on proliferation of RPMI8226 cells was evaluated by means of MTT assay. Cytotoxic effect and apoptosis was identified and analyzed with the aid of transmission electron microscopy, mitochondria membrane potential (MMP) and DNA gel electrophoresis. Meanwhile, Western-blot assay was used to detect the changes of several key cell apoptosis regulatory proteins such as BAX, caspase-3 and caspase-8 in these cells before and after treatment. The results showed that low concentrations of gossypol acetic acid (> 16 micromol/L) could suppress the proliferation and induce the apoptosis in RPMI8226 cells effectively. At the same time, gossypol acetic acid could also down-regulate the mitochondrial membrane potential, up-regulate the expression of the apoptosis-related protein such as BAX and caspase-3. It is concluded that the gossypol acetic acid can selectively induce proliferation inhibition and apoptosis of multiple myeloma RPMI8226 cells with a smaller dose.
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PMID:[Apoptosis of multiple myeloma cells induced by gossypol acetic acid in vitro and its mechanism]. 2003 Sep 26


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