Bcl-2 but not clusterin/apolipoprotein J protected human diploid fibroblasts and immortalized keratinocytes from ceramide-induced apoptosis: role of p53 in the ceramide response |
| |
Authors: | Kolettas Evangelos Skoufos Ioannis Kontargiris Evangelos Markopoulou Soultana Tzavaras Theodoros Gonos Efstathios S |
| |
Affiliation: | Cell and Molecular Physiology Unit, Laboratory of Experimental Physiology, University of Ioannina Medical School, 45 110 Ioannina, Greece. ekoletas@cc.uoi.gr |
| |
Abstract: | The role of clusterin/apolipoprotein J (Clu/ApoJ) and Bcl-2 on C(2)-ceramide-induced apoptosis of embryonic human diploid fibroblasts, MRC-5 and immortalized adult skin keratinocytes, HaCaT was investigated. C(2)-ceramide-induced apoptosis of HaCaT in a time- and dose-dependent manner, while in MRC-5 only at higher concentrations. There was a dose-dependent accumulation of Clu/ApoJ and downregulation of Bcl-2 which correlated with C(2)-ceramide-induced apoptosis of MRC-5. While overexpression of Bcl-2 suppressed C(2)-ceramide-mediated apoptosis in both cell types, Clu/ApoJ failed to do so, accessed by morphological changes, DNA fragmentation and PARP cleavage. There was no change in the expression of endogenous p53 or p21(Waf1/Cip1) upon C(2)-ceramide treatment of MRC-5. However, mutant p53(143ala) increased the sensitivity of MRC-5 to C(2)-ceramide-induced apoptosis by markedly downregulating Bcl-2, pointing to a role for p53. These results suggested that whereas downregulation of Bcl-2 may be a crucial factor involved in C(2)-ceramide-induced apoptosis, accumulation of Clu/ApoJ may be a signal of stress response. Moreover, the ceramide-activated apoptotic pathway may be regulated by p53. |
| |
Keywords: | Human fibroblasts Keratinocytes C2-ceramide Cell proliferation Apoptosis Bcl-2 Clusterin/apolipoprotein J p53 |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|