大野 秀樹
Department School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine Position Assistant Professor |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA |
Journal | Formal name:J Biol Chem ISSN code:0021-9258 (Print) 0021-9258 (Linking) |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 278,pp.25585-25590 |
Author and coauthor | Suzuki, J Ohnishi, H Wada, A Hirayama, T Ohno, H Ueda, N Yasuda, H Iiri, T Wada, Y Futai, M Mashima, H |
Publication date | 2003 |
Summary | The Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. The formed vacuole is assumed to be a hybrid of late endosome and lysosome. To elucidate the molecular mechanism of VacA-induced vacuolation, we examined the participation of syntaxin 7 in the human gastric epithelial cell line AGS. Immunocytochemistry revealed that endogenous syntaxin 7 was localized to vacuoles induced by VacA. Northern and Western blotting demonstrated that VacA intoxication increased syntaxin 7 mRNA and protein expression, respectively, in a time-dependent manner. Transient transfection of dominant-negative mutant syntaxin 7, which lacks a carboxyl-terminal transmembrane domain, inhibited VacA-induced vacuolation. In contrast, transient transfection of wild-type syntaxin 7, dominant-negative mutant syntaxin 1a, or dominant-negative mutant syntaxin 4 did not alter VacA-induced vacuolation. Furthermore, under VacA treatment, neutral red dye uptake, a parameter of VacA-induced vacuolation, was inhibited in cells stably transfected with mutant syntaxin 7 but not in cells stably transfected with wild-type syntaxin 7, mutant syntaxin 1a, or mutant syntaxin 4. Sequential immunocytochemical observation confirmed that expression of mutant syntaxin 7 did not affect VacA attachment to or internalization into AGS cells. We suggest that syntaxin 7 is involved in the intracellular vacuolation induced by VacA. |
DOI | 10.1074/jbc.M212445200 |
Document No. | 12730232 |