Article ; Online: M-COPA, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin.
Genes to cells : devoted to molecular & cellular mechanisms
2016 Volume 21, Issue 8, Page(s) 901–906
Abstract: ... that 2-methylcoprophilinamide (M-COPA), a compound that induces disassembly of the Golgi apparatus ... by inactivating ADP-ribosylation factor 1 (Arf1), suppresses Stx-induced apoptosis. M-COPA inhibited transport ... by M-COPA could be a novel approach to suppress Stx toxicity. ...
Abstract | Shiga toxin (Stx) is a main virulence factor of Stx-producing Escherichia coli (STEC) that contributes to diarrhea and hemorrhagic colitis and occasionally to fatal systemic complications. Therefore, the development of an antidote to neutralize Stx toxicity is urgently needed. After internalization into cells, Stx is transferred to the Golgi apparatus via a retrograde vesicular transport system. We report here that 2-methylcoprophilinamide (M-COPA), a compound that induces disassembly of the Golgi apparatus by inactivating ADP-ribosylation factor 1 (Arf1), suppresses Stx-induced apoptosis. M-COPA inhibited transport of Stx from the plasma membrane to the Golgi apparatus and suppressed degradation of anti-apoptotic proteins and the activation of caspases. These findings suggest that inhibition of Stx retrograde transport by M-COPA could be a novel approach to suppress Stx toxicity. |
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MeSH term(s) | ADP-Ribosylation Factor 1/antagonists & inhibitors ; ADP-Ribosylation Factor 1/genetics ; Alkenes/chemistry ; Alkenes/pharmacology ; Antidotes/chemistry ; Antidotes/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Colitis/drug therapy ; Colitis/microbiology ; Diarrhea/drug therapy ; Diarrhea/microbiology ; Golgi Apparatus/drug effects ; Humans ; Naphthols/administration & dosage ; Pyridines/administration & dosage ; Shiga Toxin/antagonists & inhibitors ; Shiga Toxin/toxicity ; Shiga-Toxigenic Escherichia coli/drug effects ; Shiga-Toxigenic Escherichia coli/pathogenicity |
Chemical Substances | Alkenes ; Antidotes ; N-(pyridine-3-ylmethyl)-5-(7-hydroxy-2,6,8-trimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalene-1-yl)-2-methylpenta-2,4-dienamide ; Naphthols ; Pyridines ; coprophilin ; Shiga Toxin (75757-64-1) ; ADP-Ribosylation Factor 1 (EC 3.6.5.2) |
Language | English |
Publishing date | 2016-08 |
Publishing country | England |
Document type | Journal Article |
ZDB-ID | 1330000-3 |
ISSN | 1365-2443 ; 1356-9597 |
ISSN (online) | 1365-2443 |
ISSN | 1356-9597 |
DOI | 10.1111/gtc.12386 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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