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Decreased Mitochondrial Membrane Potential (decreased + mitochondrial_membrane_potential)
Selected Abstracts2-(4-methylphenyl)-1,3-selenazol-4-one induces apoptosis by different mechanisms in SKOV3 and HL 60 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006Hak Jun Ahn Abstract We examined the ability of the synthetic selenium compound, 2-(4-methylphenyl)-1,3-selenazol-4-one (hereafter designated 3a), to induce apoptosis in a human ovarian cancer cell line (SKOV3) and a human leukemia cell line (HL-60). Flow cytometry showed that 3a treatment induced apoptosis in both cell lines to degrees comparable to that of the positive control, paclitaxel. Apoptosis was measured by PS externalization, DNA fragmentation and decreased mitochondrial membrane potential (MMP). However, analysis of the mechanism of action revealed differences between the responses of the two cell lines. Treatment with 3a arrested the cell cycle and induced caspase-3 activation in HL-60 cells, but not in SKOV3 cells. In contrast, 3a treatment induced apoptosis through translocation of AIF, a novel pro-apoptotic protein, in SKOV3 cells, but not in HL-60 cells. Collectively, our data demonstrated that 3a induced apoptosis in both cell lines, but via different action mechanisms. J. Cell. Biochem. 99: 807,815, 2006. © 2006 Wiley-Liss, Inc. [source] S -Allyl cysteine, S -ethyl cysteine and S -propyl cysteine alleviate oxidative stress-induced damage within PC12 cellsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 14 2008Chiu-mei Chen Abstract BACKGROUND: The PC12 cell line is a suitable model for the investigation of neurodegenerative diseases. In this study, PC12 cells were used to examine in vitro antioxidative and antiapoptotic protection by S -allyl cysteine (SAC), S -ethyl cysteine (SEC) and S -propyl cysteine (SPC). PC12 cells were treated with these agents at 5 and 10 µmol L,1 before exposure to hydrogen peroxide (H2O2). RESULTS: H2O2 treatment significantly decreased mitochondrial membrane potential (MMP) and cell viability and increased lactate dehydrogenase (LDH) release and DNA fragmentation (P < 0.05). The pre-treatments with SAC, SEC and SPC significantly and concentration-dependently elevated cell viability and MMP and lowered LDH release and DNA fragmentation (P < 0.05). H2O2 treatment also significantly increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and oxidised glutathione (GSSG) and decreased glutathione (GSH) content (P < 0.05). The pre-treatments with SAC, SEC and SPC significantly decreased subsequent H2O2 -induced formation of MDA, ROS and GSSG (P < 0.05) and also alleviated H2O2 -induced GSH depletion (P < 0.05). Finally, H2O2 treatment significantly decreased Na+ -K+ -ATPase activity and elevated caspase-3 activity (P < 0.05). The pre-treatments with SAC, SEC and SPC significantly attenuated H2O2 -induced Na+ -K+ -ATPase activity reduction and caspase-3 activity elevation (P < 0.05). CONCLUSION: The results obtained support that the three cysteine-containing compounds studied are potent neuroprotective agents. Copyright © 2008 Society of Chemical Industry [source] 1,1-bis(3,-indolyl)-1-(p- substituted phenyl)methanes decrease mitochondrial membrane potential and induce apoptosis in endometrial and other cancer cell linesMOLECULAR CARCINOGENESIS, Issue 7 2008Jun Hong Abstract 1,1-Bis(3,-indolyl)-1-(p -substituted phenyl)methanes, containing p-t- butyl (DIM-C-pPhtBu) and phenyl (DIM-C-pPhC6H5) substituents, are peroxisome proliferator-activated receptor , (PPAR,) agonists; however, DIM-C-pPhtBu-induced growth inhibition and cell death in human HEC1A endometrial cancer cells is PPAR,-independent. DIM-C-pPhtBu decreased mitochondrial membrane potential (MMP) and promoted the release of cytochrome c and caspase activation and nuclear uptake of endonuclease G leading to apoptosis of HEC1A cells. DIM-C-pPhtBu specifically targeted the mitochondrial permeability transition pore complex (PTPC) because the DIM-C-pPhtBu-induced pro-apoptotic responses were inhibited by atractyloside (Atra), a compound that specifically interacts with the inner mitochondrial membrane adenine nucleotide transport (ANT) proteins. At the dose of Atra used in this study (300 µM), this compound alone did not alter the PTPC but inhibited the mitochondriotoxic effects of DIM-C-pPhtBu. DIM-C-pPhtBu/DIM-C-pPhC6H5 and Atra also differentially affected the ability of eosin-5-maleimide (EMA) to alkylate Cys160 in the ANT protein and Atra, but not DIM-C-pPhtBu, inhibited the exchange of ATP/ADP in isolated mitochondria suggesting that these pharmacophores act on different sites on the ANT protein. Results of this study show that the receptor-independent proapoptotic activity of DIM-C-pPhtBu and DIM-C-pPhC6H5 were related to novel mitochondriotoxic activities involving inner mitochondrial ANT proteins. © 2007 Wiley-Liss, Inc. [source] 1,1-bis(3,-indolyl)-1-(p -methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cellsMOLECULAR CARCINOGENESIS, Issue 4 2008Sung Dae Cho Abstract 1,1-Bis(3,-indolyl)-1-(p -methoxyphenyl)methane (DIM-C-pPhOCH3) is a methylene-substituted diindolylmethane (C-DIM) analog that activates the orphan receptor nerve growth factor-induced-B, (NGFI-B,, Nur77). RNA interference studies with small inhibitory RNA for Nur77 demonstrate that DIM-C-pPhOCH3 induces Nur77-dependent and -independent apoptosis, and this study has focused on delineating the Nur77-independent proapoptotic pathways induced by the C-DIM analog. DIM-C-pPhOCH3 induced caspase-dependent apoptosis in RKO colon cancer cells through decreased mitochondrial membrane potential which is accompanied by increased mitochondrial bax/bcl-2 ratios and release of cytochrome c into the cytosol. DIM-C-pPhOCH3 also induced phosphatidylinositol-3-kinase-dependent activation of early growth response gene-1 which, in turn, induced expression of the proapoptotic nonsteroidal anti-inflammatory drug-activated gene-1 (NAG1) in RKO and SW480 colon cancer cells. Moreover, DIM-C-pPhOCH3 also induced NAG-1 expression in colon tumors in athymic nude mice bearing RKO cells as xenografts. DIM-C-pPhOCH3 also activated the extrinsic apoptosis pathway through increased phosphorylation of c- jun N-terminal kinase which, in turn, activated C/EBP homologous transcription factor (CHOP) and death receptor 5 (DR5). Thus, the effectiveness of DIM-C-pPhOCH3 as a tumor growth inhibitor is through activation of Nur77-dependent and -independent pathways. © 2007 Wiley-Liss, Inc. [source] Development of an in vitro cell culture model of hepatic steatosis using hepatocyte-derived reporter cells,BIOTECHNOLOGY & BIOENGINEERING, Issue 5 2009Amol V. Janorkar Abstract Fatty liver disease is a problem of growing clinical importance due to its association with the increasingly prevalent conditions of obesity and diabetes. While steatosis represents a reversible state of excess intrahepatic lipid, it is also associated with increased susceptibility to oxidative and cytokine stresses and progression to irreversible hepatic injury characterized by steatohepatitis, cirrhosis, and malignancy. Currently, the molecular mechanisms underlying progression of this dynamic disease remain poorly understood, particularly at the level of transcriptional regulation. We recently constructed a library of stable monoclonal green fluorescent protein (GFP) reporter cells that enable transcriptional regulation to be studied dynamically in living cells. Here, we adapt the reporter cells to create a model of steatosis that will allow investigation of transcriptional dynamics associated with the development of steatosis and the response to subsequent "second hit" stresses. The reporter model recapitulates many cellular features of the human disease, including fatty acid uptake, intracellular triglyceride accumulation, increased reactive oxygen species accumulation, decreased mitochondrial membrane potential, increased susceptibility to apoptotic cytokine stresses, and decreased proliferation. Finally, to demonstrate the utility of the reporter cells for studying transcriptional regulation, we compared the transcriptional dynamics of nuclear factor ,B (NF,B), heat shock response element (HSE), and glucocorticoid response element (GRE) in response to their classical inducers under lean and fatty conditions and found that intracellular lipid accumulation was associated with dose-dependent impairment of NF,B and HSE but not GRE activation. Thus, steatotic reporter cells represent an efficient model for studying transcriptional responses and have the potential to provide important insights into the progression of fatty liver disease. Biotechnol. Bioeng. 2009;102: 1466,1474. © 2008 Wiley Periodicals, Inc. [source] The novel ruthenium,, -linolenic complex [Ru2(aGLA)4Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential, increased reactive oxygen species generation and apoptosis in vitroCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2010Geise Ribeiro Abstract The present study reports the synthesis of a novel compound with the formula [Ru2(aGLA)4Cl] according to elemental analyses data, referred to as Ru2GLA. The electronic spectra of Ru2GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru2GLA was synthesized with the aim of combining and possibly improving the anti-tumour properties of the two active components ruthenium and , -linolenic acid (GLA). The properties of Ru2GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru2GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru2GLA enters the cells and ICP-AES elemental analysis found an increase in ruthenium from <0.02 to 425,mg/Kg in treated cells. The sub-G1 apoptotic cell population was increased by Ru2GLA (22,±,5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru2GLA (44,±,2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18,±,1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru2GLA exposed cells. The EC50 for Ru2GLA decreased with increasing time of exposure from 285,µM at 24,h, 211,µM at 48,h to 81,µM at 72,h. In conclusion, Ru2GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright © 2009 John Wiley & Sons, Ltd. [source] The phosphatidylinositol 3-kinase,Akt pathway protects cardiomyocytes from ischaemic and hypoxic apoptosis via mitochondrial functionCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2010Hua-Pei Song Summary 1.,After a severe burn, a marked decrease in myocardial blood flow results in ischaemic and hypoxic injury, which subsequently leads to apoptosis or necrosis. Phosphatidylinositol 3-kinase (PI3-K)/Akt is an important intracellular signal transduction molecule that regulates cell proliferation, differentiation, glucose metabolism and migration. However, the function and mechanisms of the PI3-K,Akt pathway in cardiomyocyte apoptosis after a burn remain unclear. 2.,In the present study, an in vivo rat model of burn injury and an in vitro hypoxic model using rat cardiomyocytes were established. In burned rats, the expression of PI3-K and phosphorylated (p-) Akt expression increased, as did myocardial apoptosis. Inhibition of the PI3-K,Akt pathway with 1.4 mg/kg LY294002 caused a significant increase in the myocardial apoptotic index compared with hypoxia alone in the in vivo model. 3.,Cardiomyocytes cultured under hypoxic conditions exhibited increased apoptosis, decreased cell viability, enhanced caspase 3 activity, a decreased mitochondrial membrane potential, increased cytoplasmic calcium transients and increased p53 and Bax mRNA expression. Pretreatment with 50 ,mol/L LY294002 significantly enhanced all these negative indicators compared with hypoxia alone. In contrast, pretreatment of cells with 200 ng/mL insulin-like growth factor-1, an activator of PI3-K,Akt, significantly ameliorated the effects of hypoxia, although control levels were not reached. 4.,These findings indicate that activation of the PI3-K,Akt pathway induced by ischaemia and hypoxia after a severe burn can protect cardiomyocytes from apoptosis. This anti-apoptotic effect is most likely mediated via the mitochondria and changes in p53 and Bax gene expression, intracellular [Ca2+] and caspase 3 activity. [source] | |||||||||||||