論文 - 詳細
| RRC ID | 42893 |
|---|---|
| 著者 | Yang D, Yaguchi T, Yamamoto H, Nishizaki T. |
| タイトル | Intracellularly transported adenosine induces apoptosis in HuH-7 human hepatoma cells by downregulating c-FLIP expression causing caspase-3/-8 activation. |
| ジャーナル | Biochem Pharmacol |
| Abstract |
Extracellular adenosine induced apoptosis of HuH-7 cells, a Fas-deficient human hepatoma cell line. The adenosine action was inhibited by dipyridamole, an adenosine transporter inhibitor, or 5'-amino-5'-deoxyadenosine, an inhibitor of adenosine kinase to convert from adenosine to AMP, but it was not affected by inhibitors for adenosine A(1), A(2a), A(2b), and A(3) adenosine receptors. Adenosine activated caspase-3 and -8, but not caspase-9, in HuH-7 cells, and the activation was abolished by dipyridamole. In the real-time RT-PCR and Western blot analysis, extracellular adenosine downregulated mRNA and protein levels for c-FLIP, and the effect was suppressed by dipyridamole. Furthermore, overexpression of c-FLIP short in HuH-7 cells inhibited adenosine-induced caspase-8 activity. Taken together, these results suggest that intracellularly transported adenosine, perhaps converted AMP as the ensuing event, activates caspase-8 and the downstream effector caspase caspase-3 by neutralizing caspase-8 inhibition due to c-FLIP as a consequence of decreased c-FLIP expression, leading to apoptosis. This extends our understanding of adenosine-induced molecular apoptotic pathways. |
| 巻・号 | 73(10) |
| ページ | 1665-75 |
| 公開日 | 2007-5-15 |
| DOI | 10.1016/j.bcp.2007.01.020 |
| PII | S0006-2952(07)00025-1 |
| PMID | 17303086 |
| MeSH | Adenosine / metabolism* Apoptosis / physiology* Biological Transport / physiology* CASP8 and FADD-Like Apoptosis Regulating Protein / genetics CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism* Carcinoma, Hepatocellular / pathology* Caspase 3 / metabolism* Caspase 8 / metabolism* Down-Regulation Enzyme Activation Gene Expression Humans Liver Neoplasms / pathology Tumor Cells, Cultured |
| IF | 4.96 |
| 引用数 | 42 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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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| 最多言及媒体 | Youtube |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |