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Potential Mechanisms Involved in Ceramide-induced Apoptosis in Human Colon Cancer HT29 Cells 被引量:4
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作者 JING WANG xiao-wen lv AND Yu-Guo DU 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2009年第1期76-85,共10页
Objective To investigate the potential mechanisms of cell death after the treatment with ceramide. Methods MTT assay, DNA ladder, reporter assay, FACS and Western blot assay were employed to investigate the potential ... Objective To investigate the potential mechanisms of cell death after the treatment with ceramide. Methods MTT assay, DNA ladder, reporter assay, FACS and Western blot assay were employed to investigate the potential mechanisms of cell death after the treatment with C2-ceramide. Results A short-time treatment with C2-ceramide induced cell death, which was associated with p38 MAP kinase activation, but had no links with typical caspase activation or PARP degradation. Rather than caspase inhibitor, Inhibitor of p38 MAP kinase blocked cell death induced by a short-time treatment with ceramide (〈12 h). However, inhibition of p38 MAP kinase could not block cell death induced by a prolonged treatment with ceramide (〉12 h). Moreover, incubation of cells with ceramide for a long time (〉12 h) increased subG1, but reduced S phase accompanied by caspase-dependent and caspase-independent changes including NFr, B activation. Conclusion Ceramide-induced cell apoptosis involves both caspase-dependent and -independent signaling pathway. Caspase-independent cell death occurring in a relatively early stage, which is mediated via p38 MAP kinase, can progress into a stage involving both caspase-dependent and -independent mechanisms accompanied by cell signaling of MAPKs and NFκB. 展开更多
关键词 CERAMIDE HT29 cells APOPTOSIS Cell signaling p38 MAPK NFΚB
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Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells 被引量:3
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作者 Jing Wang xiao-wen lv +1 位作者 Jie-Ping Shi Xiao-Song Hu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第7期1129-1134,共6页
AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium ... AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by indudng cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERKl/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARy was upregulated. Addition of GW9662, which is a PPARy specific antagonist, could reserve the modulation action on CDK7. CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARy activation. The ERK signaling pathway was involved in this process. 展开更多
关键词 CERAMIDE Cell cycle arrest Humanhepatocarcinoma cells P21 CyclinD1 CDK7 PPARY ERK
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