| 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
|
| リソース情報 |
| ヒト・動物細胞 |
CACO-2(RCB0988)
HeLa |
