論文 - 詳細
| RRC ID | 6827 |
|---|---|
| 著者 | Matsuda S, Kodama T, Okada N, Okayama K, Honda T, Iida T. |
| タイトル | Association of Vibrio parahaemolyticus thermostable direct hemolysin with lipid rafts is essential for cytotoxicity but not hemolytic activity. |
| ジャーナル | Infect Immun |
| Abstract |
Thermostable direct hemolysin (TDH), a major virulence factor of Vibrio parahaemolyticus, induces cytotoxicity in cultured cells. However, the mechanism of TDH's cytotoxic effect including its target molecules on the plasma membrane of eukaryotic cells remains unclear. In this study, we identified the role of lipid rafts, cholesterol- and sphingolipid-enriched microdomains, in TDH cytotoxicity. Treatment of cells with methyl-beta-cyclodextrin (MbetaCD), a raft-disrupting agent, inhibited TDH cytotoxicity. TDH was associated with detergent-resistant membranes (DRMs), and MbetaCD eliminated this association. In contrast, there was no such association between a nontoxic TDH mutant and DRMs. The disruption of lipid rafts neither affected hemolysis nor inhibited Ca(2+) influx into HeLa cells induced by TDH. These findings indicate that the cytotoxicity but not the hemolytic activity of TDH is dependent on lipid rafts. The exogenous and endogenous depletion of cellular sphingomyelin also prevented TDH cytotoxicity, but a direct interaction between TDH and sphingomyelin was not detected with either a lipid overlay assay or a liposome absorption test. Treatment with sphingomyelinase (SMase) at 100 mU/ml disrupted the association of TDH with DRMs but did not affect the localization of lipid raft marker proteins (caveolin-1 and flotillin-1) with DRMs. These results suggest that sphingomyelin is important for the association of TDH with lipid rafts but is not a molecular target of TDH. We hypothesize that TDH may target a certain group of rafts that are sensitive to SMase at a certain concentration, which does not affect other types of rafts. |
| 巻・号 | 78(2) |
| ページ | 603-10 |
| 公開日 | 2010-2-1 |
| DOI | 10.1128/IAI.00946-09 |
| PII | IAI.00946-09 |
| PMID | 19933828 |
| PMC | PMC2812206 |
| MeSH | Animals Bacterial Proteins / metabolism* Bacterial Toxins / metabolism Cell Line Erythrocytes / microbiology Erythrocytes / pathology HeLa Cells Hemolysin Proteins / metabolism* Hemolysis / physiology* Humans Membrane Microdomains / metabolism* Sphingomyelins / metabolism Vibrio parahaemolyticus / metabolism Vibrio parahaemolyticus / pathogenicity* |
| IF | 3.201 |
| 引用数 | 37 |
| WOS 分野 | INFECTIOUS DISEASES IMMUNOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | LY-A/hCERT(RCB1870) LY-B(RCB1698) LY-B/cLCB1(RCB1699) |