論文 - 詳細
| RRC ID | 44307 |
|---|---|
| 著者 | Sawai H. |
| タイトル | Differential effects of caspase inhibitors on TNF-induced necroptosis. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
TNF has been reported to induce caspase-independent necroptosis in the presence of Z-VAD-fmk, a pan-caspase inhibitor. We examined whether necroptosis was induced by caspase inhibitors other than Z-VAD-fmk. TNF-induced necroptosis was detected in the presence of Z-DEVD-fmk, which is commonly used as a caspase-3-specific inhibitor, but not in the presence of Z-Asp-CH2-DCB, which was reported to be a pan-caspase inhibitor. TNF-induced caspase-3 activity was completely inhibited by Z-VAD-fmk, Z-DEVD-fmk, or Z-Asp-CH2-DCB. Although TNF-induced proteolytic activation of procaspase-3 was completely prevented by Z-VAD-fmk or Z-DEVD-fmk, the partial proteolysis of procaspase-3 was induced in the presence of Z-Asp-CH2-DCB. Furthermore, although TNF-induced proteolytic activation of procaspase-8 was completely inhibited by Z-VAD-fmk or Z-DEVD-fmk, the partial proteolysis of procaspase-8 to the p43/41 intermediate and p18 active fragment was detected in the presence of Z-Asp-CH2-DCB. The cleavage of RIP1, which plays a crucial role in TNF-induced necroptosis and is cleaved by caspase-8, was completely inhibited by Z-VAD-fmk or Z-DEVD-fmk, whereas the partial degradation of RIP1 was detected in the presence of Z-Asp-CH2-DCB. These results suggest that the partial activation of caspase-8 in the presence of Z-Asp-CH2-DCB may suppress TNF-induced necroptosis via the cleavage of RIP1, and also suggest that Z-Asp-CH2-DCB, but not Z-DEVD-fmk, may be used as a caspase-3-specific inhibitor in cells. |
| 巻・号 | 432(3) |
| ページ | 451-5 |
| 公開日 | 2013-3-15 |
| DOI | 10.1016/j.bbrc.2013.01.126 |
| PII | S0006-291X(13)00245-3 |
| PMID | 23410748 |
| MeSH | Amino Acid Chloromethyl Ketones / pharmacology* Apoptosis / drug effects* Aspartic Acid / analogs & derivatives* Aspartic Acid / pharmacology Caspase 3 / metabolism* Caspase 8 / metabolism* Caspase Inhibitors / pharmacology* Cell Line, Tumor Humans Necrosis / enzymology* Nuclear Pore Complex Proteins / metabolism Oligopeptides / pharmacology* Proteolysis RNA-Binding Proteins / metabolism Tumor Necrosis Factor-alpha / pharmacology* |
| IF | 2.985 |
| 引用数 | 12 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | |