論文 - 詳細
| RRC ID | 42856 |
|---|---|
| 著者 | Katayama H, Kusaka Y, Yokota H, Akao T, Kojima M, Nakamura O, Mekada E, Mizuki E. |
| タイトル | Parasporin-1, a novel cytotoxic protein from Bacillus thuringiensis, induces Ca2+ influx and a sustained elevation of the cytoplasmic Ca2+ concentration in toxin-sensitive cells. |
| ジャーナル | J Biol Chem |
| Abstract |
Parasporin-1 is a novel non-insecticidal inclusion protein from Bacillus thuringiensis that is cytotoxic to specific mammalian cells. In this study, we investigated the effects of parasporin-1 on toxin-sensitive cell lines to elucidate the cytotoxic mechanism of parasporin-1. Parasporin-1 is not a membrane pore-forming toxin as evidenced by measurements of lactate dehydrogenase release, propidium iodide penetration, and membrane potential in parasporin-1-treated cells. Parasporin-1 decreased the level of cellular protein and DNA synthesis in parasporin-1-sensitive HeLa cells. The earliest change observed in cells treated with this toxin was a rapid elevation of the intracellular free-Ca(2+) concentration; increases in the intracellular Ca(2+) levels were observed 1-3 min following parasporin-1 treatment. Using four different cell lines, we found that the degree of cellular sensitivity to parasporin-1 was positively correlated with the size of the increase in the intracellular Ca(2+) concentration. The toxin-induced elevation of the intracellular Ca(2+) concentration was markedly decreased in low-Ca(2+) buffer and was not observed in Ca(2+)-free buffer. Accordingly, the cytotoxicity of parasporin-1 decreased in the low-Ca(2+) buffer and was restored by the addition of Ca(2+) to the extracellular medium. Suramin, which inhibits trimeric G-protein signaling, suppressed both the Ca(2+) influx and the cytotoxicity of parasporin-1. In parasporin-1-treated HeLa cells, degradation of pro-caspase-3 and poly(ADP-ribose) polymerase was observed. Furthermore, synthetic caspase inhibitors blocked the cytotoxic activity of parasporin-1. These results indicate that parasporin-1 activates apoptotic signaling in these cells as a result of the increased Ca(2+) level and that the Ca(2+) influx is the first step in the pathway that underlies parasporin-1 toxicity. |
| 巻・号 | 282(10) |
| ページ | 7742-52 |
| 公開日 | 2007-3-9 |
| DOI | 10.1074/jbc.M611382200 |
| PII | S0021-9258(20)63616-X |
| PMID | 17204466 |
| MeSH | Apoptosis / drug effects Bacillus thuringiensis / pathogenicity* Calcimycin / pharmacology Calcium / metabolism* Cell Membrane Permeability / drug effects Cytoplasm / metabolism* DNA / biosynthesis Endotoxins / pharmacology* HeLa Cells Humans Ionomycin / pharmacology Protein Biosynthesis / drug effects Suramin / pharmacology |
| IF | 4.238 |
| 引用数 | 28 |
| WOS 分野 | 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 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 | CACO-2(RCB0988) HeLa |