論文 - 詳細
| RRC ID | 38277 |
|---|---|
| 著者 | Yang D, Yaguchi T, Nakano T, Nishizaki T. |
| タイトル | Adenosine-induced caspase-3 activation by tuning Bcl-XL/DIABLO/IAP expression in HuH-7 human hepatoma cells. |
| ジャーナル | Cell Biol Toxicol |
| Abstract |
Extracellular adenosine disrupted mitochondrial membrane potentials in HuH-7 cells, a Fas-deficient human hepatoma cell line, and the effect was inhibited by the adenosine transporter inhibitor dipyridamole or by overexpressing Bcl-X(L). Adenosine downregulated the expression of mRNAs and proteins for Bcl-X(L) and inhibitor of apoptosis protein 2 (IAP2) to directly inhibit caspase-3, -7, and -9, but it otherwise upregulated the expression of mRNA and protein for DIABLO, an inhibitor of IAPs. Those adenosine effects were attenuated by dipyridamole. Caspase-3 and -8 were implicated in adenosine-induced HuH-7 cell death, and adenosine actually activated caspase-3 without caspase-9 activation. The caspase-3 activation was inhibited by overexpressing Bcl-X(L) or IAP2. Taken together, the results of the present study indicate that intracellularly transported adenosine activates caspase-3 by neutralizing caspase-3 inhibition due to IAP as a result of decreased IAP2 expression and reduced IAP activity in response to increased DIABLO expression and perhaps DIABLO release from damaged mitochondria, in addition to caspase-8 activation. This represents further insight into adenosine-induced HuH-7 cell apoptotic pathway. |
| 巻・号 | 26(4) |
| ページ | 319-30 |
| 公開日 | 2010-8-1 |
| DOI | 10.1007/s10565-009-9145-7 |
| PMID | 20063052 |
| MeSH | Adenosine / pharmacology* Apoptosis Regulatory Proteins Baculoviral IAP Repeat-Containing 3 Protein Biological Transport / drug effects Blotting, Western Carcinoma, Hepatocellular / enzymology* Carcinoma, Hepatocellular / genetics Caspase 3 / metabolism* Caspase 9 / metabolism Cell Line, Tumor Down-Regulation / drug effects Enzyme Activation / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Intracellular Space / drug effects Intracellular Space / metabolism Liver Neoplasms / enzymology* Liver Neoplasms / genetics Membrane Potential, Mitochondrial / drug effects Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Protease Inhibitors / pharmacology RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects Ubiquitin-Protein Ligases Up-Regulation / drug effects bcl-X Protein / genetics bcl-X Protein / metabolism* |
| IF | 6.284 |
| 引用数 | 23 |
| WOS 分野 | TOXICOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1648) |