論文 - 詳細
| RRC ID | 38486 |
|---|---|
| 著者 | Okumura S, Saitoh H, Ishikawa T, Inouye K, Mizuki E. |
| タイトル | Mode of action of parasporin-4, a cytocidal protein from Bacillus thuringiensis. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
Parasporin-4 (PS4) is a cytotoxic protein produced by Bacillus thuringiensis strain A1470. It exhibits specific cytotoxicity against human cancer cell lines, CACO-2, Sawano, and MOLT-4 cells, in particular. When cells were administrated with PS4, cell swelling and nuclear shrinkage were induced, and, the ballooned cells burst within 24 h. PSI-BLAST search showed that the protein shared homology not only with B. thuringiensis Cry toxins but also with aerolysin-type β-pore-forming toxins. Circular dichroism measurements suggested that PS4 was a β-sheet-rich protein. PS4 aggregated into oligomers on the plasma membrane of PS4-susceptible CACO-2 cells, but not on that of PS4-resistant HeLa cells. Leakage of lactate dehydrogenase and influx of extracellular FITC-dextrans were observed only in susceptible cells. The activation of effectors caspase 3 and/or 7 was not observed in PS4-treated CACO-2 cells. It was shown that cytotoxicity of the PS4 against CACO-2 cells was exhibited when treated by cyclodextrin which induces cholesterol depletion. These results suggest that PS4 is a unique β-pore-forming toxin with a cholesterol-independent activity. |
| 巻・号 | 1808(6) |
| ページ | 1476-82 |
| 公開日 | 2011-6-1 |
| DOI | 10.1016/j.bbamem.2010.11.003 |
| PII | S0005-2736(10)00376-7 |
| PMID | 21073856 |
| MeSH | Anticholesteremic Agents / pharmacology Bacillus thuringiensis / metabolism* Bacterial Proteins / chemistry Bacterial Proteins / metabolism Bacterial Proteins / pharmacology* Caco-2 Cells Caspase 3 / metabolism Caspase 7 / metabolism Cell Line, Tumor Cell Membrane / drug effects Cell Membrane / metabolism Cell Size / drug effects Cell Survival / drug effects Cholesterol / metabolism Circular Dichroism Dose-Response Relationship, Drug Endotoxins / chemistry Endotoxins / metabolism Endotoxins / pharmacology* Enzyme Activation / drug effects Flow Cytometry HeLa Cells Humans K562 Cells L-Lactate Dehydrogenase / metabolism Lovastatin / pharmacology Microscopy, Phase-Contrast Neoplasms / metabolism Neoplasms / pathology Protein Binding Protein Multimerization |
| IF | 3.411 |
| 引用数 | 19 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) MOLT-4(RCB0206) HeLa(RCB0007) K562(RCB0027) |