Mitochondria-independent induction of Fas-mediated apoptosis by MSSP
| Autor: | Ken-ichi Matsumoto, Jun Nomura, Hiroyoshi Ariga, Sanae M.M. Iguchi-Ariga |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
RNA-Binding Proteins/physiology
Cancer Research Interferon-gamma/pharmacology Fibroblasts Thymus Gland/cytology Fas ligand Gene Expression Profiling Mice Mice Knockout Caspase 8 biology Cytochromes c/secretion Cytochrome c apoptosis Apoptosis/physiology Cytochromes c RNA-Binding Proteins General Medicine Fas receptor DNA-Binding Proteins mitochondria Oncology Caspases Antigens CD95/physiology Programmed cell death caspase Caspase 3 Thymus Gland Interferon-gamma Mitochondria/physiology MHC class I Animals Caspases/metabolism fas Receptor Fas Molecular biology DNA-Binding Proteins/physiology Apoptosis biology.protein MSSP Interleukin-1/pharmacology Antigens CD95/genetics Interleukin-1 |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1021-335X |
| Popis: | Fas-mediated apoptosis has been proposed to play an important role in homeostasis. Fas triggers apoptosis after stimulation by its ligand FasL or the Fas ligand agonist anti-Fas antibody through a mitochondria-dependent or -independent pathway, and MSSP has been identified as a transcription factor that regulates the c-myc gene and was later found to positively or negatively regulate a variety of genes, including alpha-smooth actin, MHC class I, MHC class 2 and the thyrotropin receptor. We further found that expression of the Fas gene was repressed, resulting in abrogation of the Fas-mediated induction of apoptosis both in Mssp-knockout mice and primary thymocytes. MSSP was then found to stimulate promoter activity of the Fas gene by binding to a specific region. In this study, to identify the MSSP-dependent Fas-induced apoptosis pathway, primary fibroblasts from MSSP (+/+) and MSSP (-/-) cells were treated with the combination of interleukin 1-beta and interferon-gamma and expression of the Fas gene was examined. The results showed that the Fas gene was expressed at the same levels in the two cell types. Furthermore, when these cells were treated with the anti-Fas antibody, it was found that cytochrome C was not released in the cytosol and that activations of caspase 8 and caspase 3 occurred in primary fibroblasts from MSSP (+/+) cells but not from MSSP (-/-) cells. These results indicate that Fas-mediated apoptosis induced by MSSP occurs independently of mitochondria. |
| Databáze: | OpenAIRE |
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