| Novel subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli induces apoptosis in vero cells via mitochondrial membrane damage. | |
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MedLine Citation:
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PMID: 19380466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Subtilase cytotoxin (SubAB) is an AB(5) cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone, BiP, leading to transient inhibition of protein synthesis and cell cycle arrest at G(1) phase. Here we show that SubAB, but not the catalytically inactive mutant SubAB(S272A), induced apoptosis in Vero cells, as detected by DNA fragmentation and annexin V binding. SubAB induced activation of caspase-3, -7, and -8. Caspase-3 appeared earlier than caspase-8, and by use of specific caspase inhibitors, it was determined that caspase-3 may be upstream of caspase-8. A general caspase inhibitor blocked SubAB-induced apoptosis, detected by annexin V binding. SubAB also stimulated cytochrome c release from mitochondria, which was not suppressed by caspase inhibitors. In HeLa cells, Apaf-1 small interfering RNA inhibited caspase-3 activation, suggesting that cytochrome c might form an apoptosome, leading to activation of caspase-3. These data suggested that SubAB induced caspase-dependent apoptosis in Vero cells through mitochondrial membrane damage. |
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Authors:
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Gen Matsuura; Naoko Morinaga; Kinnosuke Yahiro; Reiko Komine; Joel Moss; Hideo Yoshida; Masatoshi Noda |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2009-04-20 |
Journal Detail:
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Title: Infection and immunity Volume: 77 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-22 Completed Date: 2009-07-14 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 2919-24 Citation Subset: IM |
Affiliation:
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Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Annexin A5 / metabolism Apoptosis* Caspase 3 / metabolism Caspase 7 / metabolism Caspase 8 / metabolism Cercopithecus aethiops Cytochromes c / metabolism DNA Fragmentation Escherichia coli Proteins / toxicity* Hela Cells Humans Mitochondrial Membranes / drug effects* Shiga-Toxigenic Escherichia coli / pathogenicity* Subtilisins / toxicity* Vero Cells |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Escherichia coli Proteins; 9007-43-6/Cytochromes c; EC 3.4.21.-/Subtilisins; EC 3.4.21.-/subtilase cytotoxin, E coli; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7; EC 3.4.22.-/Caspase 8 |
| Comments/Corrections | |
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