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Stress-induced Cell Death (stress-induced + cell_death)
Selected AbstractsVascular endothelial growth factor protects hepatoma cells against oxidative stress-induced cell deathJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2006Shinji Osada Abstract Background:, The aim of the present study was to examine coordination of the vascular endothelial growth factor (VEGF) and VEGF receptor (Flk-1) system and to study control of VEGF expression by oxidative stress, which is considered a model for chronic liver disease. Methods:, Cell viability was determined by test method with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide (MTT). Expressions of cellular proteins were evaluated by western blot analysis. Results:, The c-Met tyrosine phosphorylation in PLC/PRF/5 hepatoma cells was increased by treatment with 20 ng/mL hepatocyte growth factor (HGF), and extracellular signal-regulated kinase (ERK) was also activated. Although Flk-1 was phosphorylated in response to VEGF (>50 ng/mL), phosphorylated ERK was not detected at these concentrations. A total of 5.0 and 10 µmol/L hydrogen peroxide (H2O2) caused cell death in a dose-dependent manner after 24 h. On western blot analysis at 1 h with H2O2, rapid phosphorylation of both ERK1/2 and c-Jun NH2 -terminal kinase (JNK) was observed. In the first 6 h, H2O2 induced cell death for 58.4 ± 6.8%, whereas the presence of 100 ng/mL VEGF improved the survival rate to 77.2 ± 4.2%. The VEGF significantly decreased H2O2 -induced cell death after 12 h, whereas HGF (20 ng/mL) did not have a similar effect. When cells were incubated with 5 µmol/L H2O2, expression of VEGF protein was detected. Furthermore, H2O2 -induced phosphorylation of ERK and JNK was also reduced by VEGF (100 ng/mL). In contrast, HGF did not induce phosphorylation of ERK and JNK. Conclusion:, Hepatoma cells might be able to survive under continuous oxidative stress through expression of VEGF. [source] Vitamin E protected cultured cortical neurons from oxidative stress-induced cell death through the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinaseJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Yumiko Numakawa Abstract The role of vitamin E in the CNS has not been fully elucidated. In the present study, we found that pre-treatment with vitamin E analogs including ,T (,-tocopherol), ,T3 (, -tocotrienol), ,T, and ,T3 for 24 h prevented the cultured cortical neurons from cell death in oxidative stress stimulated by H2O2, while Trolox, a cell-permeable analog of ,T, did not. The preventive effect of ,T was dependent on de novo protein synthesis. Furthermore, we found that ,T exposure induced the activation of both the MAP kinase (MAPK) and PI3 kinase (PI3K) pathways and that the ,T-dependent survival effect was blocked by the inhibitors, U0126 (an MAPK pathway inhibitor) or LY294002 (a PI3K pathway inhibitor). Interestingly, the up-regulation of Bcl-2 (survival promoting molecule) was induced by ,T application. The up-regulation of Bcl-2 did not occur in the presence of U0126 or LY294002, suggesting that ,T-up-regulated Bcl-2 is mediated by these kinase pathways. These observations suggest that vitamin E analogs play an essential role in neuronal maintenance and survival in the CNS. [source] Role of c-Fos/JunD in protecting stress-induced cell deathCELL PROLIFERATION, Issue 3 2007H. Zhou The purpose of the current study was to investigate the role of c-Fos and JunD in stress-induced cell death. Materials and methods: We exposed cultured primary mouse embryonic fibroblasts (MEF) to ultraviolet light (UV-C) or hydrogen peroxide (H2O2). Induction of c-Fos and JunD and activation of MAPK/ERK1/2 signalling in the presence or absence of a MAPK inhibitor were analyzed by western blotting. Activation of AP-1 transcription factors was detected by the electrophoretic mobility shift assay and immunoprecipitation. Cell death was measured by changes in caspase 3 activities and nuclear morphology. Effects of c-Fos and JunD expression on cell death were investigated by transfection. Results: We found that the exposure of cultured primary MEF cells to UV or H2O2 caused a significant increase in c-Fos and JunD protein levels. In addition, these two proteins formed complexes with each other and contributed to activation of AP-1 transcription complexes. More importantly, under both stress conditions, overexpression of JunD alone or overexpression of both c-Fos and JunD reduced caspase 3 activity and cell death. At the same time, UV irradiation activated the MAPK/ERK1/2 signalling pathway. The suppression of MEK1/ERK1/2 activation inhibited UV-induced expression of c-Fos and JunD and increased caspase 3 activity and cell death. Conclusion: Our results suggest that both UV and H2O2 induce the activation of c-Fos/JunD AP-1 complexes resulting in the prevention of cell death. Moreover, UV irradiation-induced increases in c-Fos/JunD expression in primary MEF cells are mediated through the activation of the MAPK/ERK1/2 signalling pathway. [source] Preconditioning protects the retinal pigment epithelium cells from oxidative stress-induced cell deathACTA OPHTHALMOLOGICA, Issue 1 2009Rajesh K. Sharma Abstract. Purpose:, The cytotoxic effects of oxidative stress, which play an important role in ocular diseases, are well known. In this study, we investigated the effect of non-lethal doses of oxidative stress on various cell functions, namely cell viability, cell attachment and cell migration in a widely used retinal pigment epithelium (RPE) cell line (ARPE-19). Methods:, A single exposure to various concentrations of hydrogen peroxide (H2O2) was used to establish a dose response for H2O2 -induced cell death. Other cellular responses, such as changes in cell attachment and migration, were monitored after exposure to increasing doses. Finally, the effects of preconditioning cells with increasing non-lethal doses of H2O2, with and without a subsequent exposure to lethal doses of H2O2, were determined. Results:, The optimum dose for inducing cell death in ARPE-19 cells was between 900 and 1000 ,m H2O2. Preconditioning the cells with 1, 10 and 50 ,m of H2O2 provided a dose-dependent protection against cell death induced by a lethal dose (900,1000 ,m) of H2O2. Preconditioning with higher doses caused cells to become more susceptible to the cytotoxic effects of the lethal dose. Although H2O2 increased cell attachment in lower doses, it induced a dose-dependent inhibition of cell attachment to the substrate in higher doses. H2O2 did not affect cell migration in sub-lethal doses. Conclusion:, Preconditioning RPE cells with limited exposure to non-lethal oxidative stress confers significant protection against subsequent H2O2 -induced cell death. It also affects cell attachment in a dose-specific manner. This finding may help in understanding the pathogenesis of diseases in which oxidative stress plays an important role and in determining the suitability of certain treatment strategies, in particular RPE transplantation in the treatment of age-related macular degeneration. [source] | |||||||||||||