論文 - 詳細
| RRC ID | 61880 |
|---|---|
| 著者 | Takagishi T, Oda M, Takehara M, Kobayashi K, Nagahama M. |
| タイトル | Oligomer formation of Clostridium perfringens epsilon-toxin is induced by activation of neutral sphingomyelinase. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
BACKGROUND:Clostridium perfringens epsilon-toxin is responsible for fatal enterotoxemia in ungulates. The toxin forms a heptamer in the lipid rafts of Madin-Darby Canine Kidney (MDCK) cells, leading to cell death. Here, we showed that epsilon-toxin requires neutral sphingomyelinase (nSMase) activity during oligomerization. METHODS:We tested the role of nSMase in the oligomerization of epsilon-toxin using specific inhibitors, knockdown of nSMase, formation of ceramide, and localization of epsilon-toxin and ceramide by immunofluorescence staining. RESULTS:Epsilon-toxin induced the production of ceramide is a dose- and time-dependent manner in ACHN cells. GW4869, an inhibitor of nSMase, inhibited ceramide production induced by the toxin. GW4869 and knockdown of nSMase blocked toxin-induced cell death and oligomer formation of epsilon-toxin. Confocal microscopy images showed that the toxin induced ceramide clustering and colocalized with ceramide. CONCLUSIONS:These results demonstrated that oligomer formation of epsilon-toxin is facilitated by the production of ceramide through activation of nSMase caused by the toxin. GENERAL SIGNIFICANCE:Inhibitors of nSMase may confer protection against infection. |
| 巻・号 | 1858(11) |
| ページ | 2681-2688 |
| 公開日 | 2016-11-1 |
| DOI | 10.1016/j.bbamem.2016.07.009 |
| PII | S0005-2736(16)30252-8 |
| PMID | 27453200 |
| MeSH | Aniline Compounds / pharmacology Animals Bacterial Toxins / chemistry* Bacterial Toxins / toxicity Benzylidene Compounds / pharmacology Cell Line Ceramides / agonists* Ceramides / biosynthesis Clostridium perfringens / chemistry Dogs Enzyme Activation / drug effects Enzyme Assays Enzyme Inhibitors / pharmacology Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / enzymology* Gene Expression Humans Madin Darby Canine Kidney Cells Membrane Microdomains / chemistry Membrane Microdomains / drug effects* Protein Multimerization RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Sphingomyelin Phosphodiesterase / antagonists & inhibitors Sphingomyelin Phosphodiesterase / genetics Sphingomyelin Phosphodiesterase / metabolism* |
| IF | 3.411 |
| リソース情報 | |
| ヒト・動物細胞 | MDCK(RCB0995) |