Induction of p21 during ceramide-mediated apoptosis in human hepatocarcinoma cells.
Ceramide acts as a mediator of programmed cell death in various cell types, but its molecular mechanisms linked to the cell cycle are poorly understood. In this study, we investigated the expression of the p21 gene and its relationship to apoptosis induced by ceramide. In SK-HEP-1 cells, the addition of C6-ceramide resulted in a dose- and time-dependent growth suppression and DNA fragmentation characteristics of apoptosis. p21 protein was induced during that process, while the protein level of p53, known as a transcriptional activator of p21, was not elevated under the same condition. This apoptotic cell death with p21 induction was also observed in the Hep 3B cells lacking functional p53 after exposure to C6-ceramide. These findings suggest that ceramide-induced apoptosis is associated with the upregulation of p21 mRNA and protein in a p53-independent pathway.
Oh
W J
WJ
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, South Korea.
Kim
W H
WH
Kang
K H
KH
Kim
T Y
TY
Kim
M Y
MY
Choi
K H
KH
D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D053938:DNA Fragmentation; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism
C493956:CDKN1A protein, human; D002518:Ceramides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C101954:N-caproylsphingosine