Exocytotic histamine release caused by the bacterial metalloprotease : identification of the target protein on the mast cell membrane
| Project/Area Number |
12670257
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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 | OKAYAMA UNIVERSITY |
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Principal Investigator |
MIYOSHI Shin-ichi Okayama University, Graduate School of Natural Science and Technology Associate Professor, 大学院・自然科学研究科, 助教授 (60182060)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Shigeo Okayama University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (40033229)
SHINODA Sumio Okayama University, Graduate School of Natural Science and Technology Professor, 大学院・自然科学研究科, 教授 (50029782)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Mast cell / Raft / Histamine / Exocytosis / Vibrio vulnificus / Human-eating bacteria / Metalloprotease / 病原ビブリオ / 病原性ビブリオ |
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| Research Abstract |
The zinc metalloprotease (VVP) secreted by Vibrio vulnificus stimulates exocytotic histamine release from rat mast cells both in vitro and in vivo. This protease consists of two functional domains : the N-terminal domain (VVP-N) catalyzing the proteolytic reaction and the C-terminal domain promoting the association with a protein substrate.
In the present study, the single zinc ion in the catalytic center was substituted by treatment with CuCl_2 or NiCl_<2->. Although Cu^<2+>-treated VVP showed sufficient histamine-releas ing activity, Ni^<2+>-treated VVP showed the less activity because of the reduced potential to attach to the target substance. Likewise, VVP-N induced histamine release in a dose- and time-dependent manner, however, Ni^<2+>-treated VVP-N revealed much less histamine-releasing activity. Taken together, the protease may stimulate histamine release through the action of the catalytic center of the N-terminal domain on the target substance(s) on the mast cell membrane.
The GPI-anchored protein has been reported to function as the receptor for exocellular stimulus. To clarify whether this protein is the target substance of VVP, the effect of the raft preparation in which the GPI-anchored protein accumulates was examined. However, any inhibitory effect on the histamine release was not observed. This finding indicates that VVP attacks the membrane protein other than the GPI-anchored protein.
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Report
(4 results)
Research Products
(16 results)
