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)

In this study, the release of mitochondrial proapoptotic intermembrane space proteins induced by exogenous C(2)-ceramide in human colon carcinoma (HT-29) cell line was investigated. HT-29 cells were treated with 12.5, 25 and 50 micromol/L C(2)-ceramide in vitro. Flow cytometer was used to detect the mitochondrial membrane potential (DeltaPhi(m)). Subcellular fractions were extracted by Mitochondrial/Cytosol Fractionation Kit after C(2)-ceramide treatment for 24 h. SDS-PAGE was used to determine the level of cytochrome c (Cyt c), high temperature requirement A2 (HtrA2) and second mitochondrial-derived activator of caspases (Smac) released from mitochondria, the expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-3 for 24 h. The results showed that DeltaPhi(m) began to decrease from 6 h after 25 and 50 micromol/L C(2)-ceramide treatment (P<0.05) and cyclosporin A (CsA) could inhibit the collapse of DeltaPhi(m) through regulating mitochondrial membrane permeability transition pore. There was no effect of C(2)-ceramide on the expression of Cyt c, HtrA2 and Smac in the total levels. 12.5, 25 and 50 micromol/L C(2)-ceramide could induce Cyt c, HtrA2 and Smac to release from mitochondria to cytosol and down-regulate the expression of XIAP (P<0.05). Also there was expression of cleaved caspase-3 with C(2)-ceramide treatment. After the treatment with caspase inhibitor, C(2)-ceramide still induced the release of Cyt c and HtrA2, but Smac did not. Therefore, C(2)-ceramide could induce apoptosis of HT-29 cells through the mitochondria pathway. The release of Cyt c, HtrA2 and Smac from mitochondria did not occur via the same mechanism, the release of Cyt c and HtrA2 was caspase-independent and the release of Smac was caspase-dependent.
 ...
PMID:Ceramide induces release of mitochondrial proapoptotic proteins in caspase-dependent and -independent manner in HT-29 cells. 1817 93

Unlike oleate and linoleate, palmitate induced mitochondrial apoptosis in GL15 glioblastoma cells. Decrease in membrane potential in a subpopulation of mitochondria of palmitate-treated cells was revealed using the 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide probe. The diminished ability to reduce a tetrazolium salt indicated an impairment of mitochondrial function. Up to 50% cytochrome c (cyt c) was detached from the inner mitochondrial membrane and released outside mitochondria in palmitate-treated cells, whereas no release was detected after oleate and linoleate treatments. Cyt c release into the cytosol was followed by caspase 3 activation. Released cyt c and caspase 3 activity were not affected by neutral and acid sphingomyelinase inhibitors and by the inhibitor of serine palmitoyltransferase cycloserine, indicating that apoptosis was independent of the ceramide pathway, nor the mitochondrial pro-apoptotic AIF or Bcl-2/Bax factors appeared to be involved in the effect. Utilization of palmitate by GL15 cells altered phospholipid composition. Cardiolipin (CL), the lipid involved in cyt c interaction with the inner mitochondrial membrane, was decreased and highly saturated. This produced an imbalance in hydrophilic/hydrophobic interactions underlying the anchorage of cyt c, by weakening the hydrophobic component and facilitating detachment of the protein and activation of downstream processes. The primary role of CL was explored by supplying GL15 with exogenous CL through a fusion process of CL liposomes with cell plasma membrane. Fused CL moved to mitochondria, as detected by nonylacridine orange probe. Enrichment of mitochondrial membranes with CL prior to palmitate treatment of cells caused decreased cyt c release and caspase 3 activity.
 ...
PMID:Loss of cardiolipin in palmitate-treated GL15 glioblastoma cells favors cytochrome c release from mitochondria leading to apoptosis. 1818 42

Polybrominated diphenyl ethers (PBDEs) are used extensively as flame-retardants and are ubiquitous in the environment and in wildlife and human tissue. Recent studies have shown that PBDEs induce neurotoxic effects in vivo and apoptosis in vitro. However, the signaling mechanisms responsible for these events are still unclear. In this study, we investigated the action of a commercial mixture of PBDEs (pentabrominated diphenyl ether, DE-71) on a human neuroblastoma cell line, SK-N-SH. A cell viability test showed a dose-dependent increase in lactate dehydrogenase leakage and 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction. Cell apoptosis was observed through morphological examination, and DNA degradation in the cell cycle and cell apoptosis were demonstrated using flow cytometry and DNA laddering. The formation of reactive oxygen species was not observed, but DE-71 was found to significantly induce caspase-3, -8, and -9 activity, which suggests that apoptosis is not induced by oxidative stress but via a caspase-dependent pathway. We further investigated the intracellular calcium ([Ca(2+)](i)) levels using flow cytometry and observed an increase in the intracellular Ca(2+) concentration with a time-dependent trend. We also found that the N-methyl d-aspartate (NMDA) receptor antagonist MK801 (3 microM) significantly reduced DE-71-induced cell apoptosis. The results of a Western blotting test demonstrated that DE-71 treatment increases the level of Bax translocation to the mitochondria in a dose-dependent fashion and stimulates the release of cytochrome c (Cyt c) from the mitochondria into the cytoplasm. Overall, our results indicate that DE-71 induces the apoptosis of [Ca(2+)](i) in SK-N-SH cells via Bax insertion, Cyt c release in the mitochondria, and the caspase activation pathway.
 ...
PMID:DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitro. 1845 45

We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)-mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min of middle cerebral artery occlusion were similar in wild-type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/-) mice. NHE1+/+ mice developed infarct volume of 57.3 +/- 8.8 mm(3) at 24 h reperfusion (Rp), which progressed to 86.1 +/- 10.0 mm(3) at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis-inducing factor (AIF), activation of caspase-3, and TUNEL-positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/- mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase-3 was significantly reduced in NHE1+/- brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up-regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis.
 ...
PMID:Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia. 1866 34

The bromobenzene (BB)-induced hepatotoxicity comes from its reactive metabolites. The efficacy of different doses of ginger (Zingiber officinalesRose) extract in alleviating hepatotoxicity was investigated in male albino rats. Oxidative stress parameters were monitored. The drugs metabolizing enzymes; cytochrome P450 and GST, pro-inflammatory marker; COX-2 and the apoptotic marker; caspase-3 were assessed. Animals were assigned to 1 of 5 groups: control group; bromobenzene (460 mg/kg BW) alone, three animal groups 3-5 treated with different doses of ethanolic ginger extract (100, 200, 300 mg/kg BW, respectively) 2 weeks prior bromobenzene (460 mg/kg BW) treatment. Rats received orally ginger extract daily for 21 days whereas bromobenzene treatment for 7 days starting from 15th day of treatment. Oral treatment of BB was found to elicit a significant decrease in the activities of the antioxidant enzymes; SOD, GPx and the GSH level, while the activities of GR and drug metabolizing enzymes; GSTs and Cyt P450 were enhanced. Also, BB-treatment resulted in a great enhanced production of nitric oxide products and activation of COX-2 and caspase-3. Pre-treatment with different doses of ginger extract prior to BB-treatment alleviated its toxic effects on the tested parameters in the three animal groups.
 ...
PMID:Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats. 1937 70

The objective of this study is as follows. Inhibitor of growth (ING) 4 is a novel member of the ING family. It has been thought to play an inhibitory role in several malignancies through its involvment in gene transcription, apoptosis, cell cycle control, and tumor angiogenesis. The involvement of ING4 in melanomagenesis remains unknown. The purpose of this study was to investigate the inhibitory effects of ING4 on melanoma and its mechanisms. The method used was to construct recombinant plasmid pcDNA3.1-ING4 and transfect it into the human melanoma cell line M14. The effects and mechanisms of ING4 on proliferation and apoptosis of M14 cells were analyzed in vitro according to MTT assay, colony formation assay, and TUNEL assay. The detection of the expression of cell cycle or apoptosis regulators in transfected M14 cells was carried out by western blot analysis. Moreover, the level of ING4 in melanoma tissues was examined by immunohistochemistry. The expression of ING4 was markedly reduced in cutaneous melanoma tissues. Overexpression of ING4 could induce growth suppression and apoptosis enhancement in M14 cells, and also induce the upregulation of p27, Bax and Cyt-c, and the downregulation of cyclinD1, SKP2, Bcl-2, and caspase-3. In conclusion, ING4, as a novel tumor suppressor, has a potential role in growth suppression and apoptosis enhancement of melanoma M14 through the activation of the mitochondrial-induced apoptotic pathway and the hindrance of cell cycle progression. The deregulation of ING4 might be involved in melanomagenesis.
 ...
PMID:Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14. 1943 Apr 1

Recently, the role of cadmium (Cd) in immunosupression has gained importance. Nevertheless, the signaling pathways underlying cadmium-induced immune cell death remains largely unclear. In accordance to our previous in vivo report, and to evaluate the further details of the mechanism, we have investigated the effects of cadmium (CdCl(2), H(2)O) on cell cycle regulation and apoptosis in splenocytes in vitro. Our results have revealed that reactive oxygen species (ROS) and p21 are involved in cell cycle arrest in a p53 independent manner but late hour apoptotic response was accompanied by the p53 up-regulation, loss of mitochondrial transmembrane potential (MTP), down-regulation of Bcl-xl, activation of caspase-3 and release of cytochrome c (Cyt c). However, pifithrin alfa (PFT-alpha), an inhibitor of p53, fails to rescue the cells from the cadmium-induced cell cycle arrest but prevents Bcl-xl down-regulation and loss of Deltapsi(m), which indicates that there is an involvement of p53 in apoptosis. In contrast, treatment with N-acetyl cysteine (NAC) can prevent cell cycle arrest and p21 up-regulation at early hours. Although it is clear that, NAC has no effect on apoptosis, p53 expression and MPT changes at late stage events. Taken together, we have demonstrated that cadmium promotes ROS generation, which potently initiates the cell cycle arrest at early hours and finally induces p53-dependent apoptosis at later part of the event.
 ...
PMID:Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. 1947 15

Apoptosis, a form of cell death, is a fundamental process for the development and maintenance of multicellular organisms that promotes the removal of damaged, senescent or unwanted cells. Induction of cancer cell apoptosis is an important strategy of anticancer therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, inhibited the growth of prostate cancer cells (LNCaP) and promoted apoptosis via mitogen-activated protein kinases (MAPKs), which are closely associated with apoptosis and survival. Melatonin treatment significantly inhibited the growth of LNCaP cells in a dose- and time-dependent manner. It clearly induced both an early stage of apoptosis (propidium iodide(-), FITC Annexin-V(+)) and a late apoptosis/secondary necrosis (propidium iodide(+) and FITC Annexin-V(+)), which indicated induction of serial stages of apoptosis in cells. Moreover, melatonin markedly activated c-JUN N-terminal kinase (JNK) and p38 kinase, whereas extracellular signal-regulated kinase (ERK) was not responsive to melatonin. Treatment with MAPK inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that melatonin-induced apoptosis was JNK- and p38-dependent, but ERK-independent. In the presence of PD98059, caspase-3 activity increased, while levels of Bax/cytochrome c (Cyt c) and Bcl-2 decreased. These effects were opposite to those observed with SP600125 and SB202190 treatments. Together, these results strongly suggest that JNK and p38 activation directly participate in apoptosis induced by melatonin. Thus, melatonin may be of promise for anti-prostate cancer strategies.
 ...
PMID:Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. 1952 39

Bone marrow mesenchymal stem cells (MSCs) have the potential to be used in the cellular therapy of solid organs. However, tissue regeneration is limited by the death of transplanted cells. One of the main mechanisms of stem cell death in transplanted organs is through ischemia. In the present study, we sought to investigate whether a plant-derived antioxidant, berberine (BBR), could protect MSCs against MSCs apoptosis in a model of ischemia consisting of serum deprivation- and hypoxia-induced apoptosis in vitro. We also investigated the potential mechanism(s) that may mediate the action of berberine. We found that berberine significantly attenuated hypoxia-induced MSC apoptosis. Further study revealed that berberine could scavenger the reactive oxygen species (ROS), inhibit the c-jun NH(2)-terminal kinase (JNK), the loss of mitochondrial membrane potential and the release of cytochrome c (Cyt C) and caspase-3. In addition, we also showed that berberine could activate phosphoinositide-3 kinase (PI3K)/Akt and that pretreatment with PI3K/Akt inhibitors prevented berberine-induced inhibition of ROS, JNK and subsequent apoptosis, suggesting that the protective effects of berberine were PI3K/Akt-dependent. Taken together, these findings reveal that berberine protects against MSC apoptosis by preventing ROS-dependent and JNK-driven cell apoptosis in a PI3K/Akt-dependent manner. These data indicate that berberine is a promising anti-apoptotic agent for improving MSC survival during cell transplantation.
 ...
PMID:Berberine protects mesenchymal stem cells against hypoxia-induced apoptosis in vitro. 1965 70

Homo sapiens longevity assurance homologue 2 (LASS2) is a novel gene isolated from a human liver cDNA library by our laboratory, and it is a human homologue of the yeast longevity assurance gene LAG1 (Saccharomyces cerevisiae longevity assurance gene). According to our previous results, LASS2 could interact with subunit c of vacuolar type H(+)-ATPase (V-ATPase), and the overexpression of LASS2 could inhibit the cell growth of a human hepatocellular carcinoma (HCC) cell line, SMMC-7721. In order to understand the role of the interaction between LASS2 and V-ATPase in HCC cell growth, we transiently transfected plasmid pCMV-HA2-LASS2 into HCCLM3, a HCC cell line without the significant expression of endogenous LASS2. The pH-sensitive fluorescence probes, BCECF and BCECF-AM, were used to measure the intracellular and extracellular H(+) concentrations of HCCLM3 cells respectively. The effect of LASS2 gene on apoptosis was evaluated with Annexin-V/FITC and propidium iodide (PI) by flow cytometry. Western blot was used to detect cytochrome c (Cyt c) in the cytosol and mitochondria, as well as pro-caspase-3 in cytosol. The results showed that the cell growth of LASS2-transfected HCCLM3 cells was significantly inhibited compared with that of the mock control. LASS2 transfection increased intracellular H(+) concentration of HCCLM3 cells, while decreased extracellular H(+) concentration. Moreover, LASS2 transfection significantly enhanced the apoptosis of HCCLM3 cells. In LASS2-transfected cells, the amounts of Cyt c increased in the cytosol, while decreased in the mitochondria. Meanwhile, the expression of pro-caspase-3 in the cytosolic extracts was decreased. These results implicate that LASS2 gene might increase intracellular H(+) of HCC cells via the interaction with V-ATPase, thereby inducing cell apoptosis through mitochondrial pathway.
 ...
PMID:[LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma]. 2057 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>