Systematic analysis on the molecular mechanism of Shiga-toxin cytotoxicity
| Project/Area Number |
16590374
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Aichi Medical University |
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Principal Investigator |
YOSHIDA Tomoaki Aichi Medical University, Dept.of Microbiology and Immunology, Assoc.Professor, 医学部, 助教授 (70210705)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Shiga toxin / Two hybrid analysis / Intracellular trafficking / Apoptosis / Protein interaction / cDNA subtraction |
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| Research Abstract |
Our previous data showed a stunning decrease of susceptibility to Shiga-toxins (Stxs) when passaged culture of human umbilical vein endothelial cells (HUVEC) with fresh ones. Since this may be reflecting certain differences of protein expression profile, cDNA libraries from fresh and passaged HUVEC were subtracted each other. Thus obtained genes were proteasome-related proteins and galectin-1in fresh cultures, and fibronectin and vimentin in passaged cultures, respectively. The relationship with the susceptibility to Stxs, however was ambiguous, when the function of each molecule was considered. Next, possible interactions of Stx2 with host-cell proteins were examined employing two-hybrid analysis. Among proteins expressed in the fresh culture of HUVEC, small glutamine-rich tetratricopeptide repeat containing-α (SGT) appeared to interact with Stx2A subunit. Notably, SGT did not show any detectable interaction with Stx2A1, which is the active form toxin after processing with furin in endosomes. These results are suggesting that Stx2A may interact with SGT during the intracellular trafficking, but not in the execution step of cytotoxicity. The suppression of SGT expression through siRNA introduction to HUVEC remarkably rescued the cells from apoptosis, supporting the idea that STG is involved in the mechanism of Stxs cytotoxicity.
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Report
(3 results)
Research Products
(17 results)
