| Project/Area Number |
18550154
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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 |
Chemistry related to living body
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| Research Institution | Saga University |
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Principal Investigator |
KODAMA Hiroaki Saga University, Chemistry, Associate Professor (80205418)
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| Co-Investigator(Kenkyū-buntansha) |
OSADA Satoshi Saga University, Chemistry, Assistant Professor (50284609)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,130,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | signal transduction / biomolecular / biological activity / protein / dimer / ヒト好中球 / 膜貫通ペプチド / GPCR / 活性酸素放出 / ペプチド合成 |
|---|
| Research Abstract |
Neutrophil functions including chemotaxis, degranulation, and generation of superoxide anion are modulated by diverse extracellular agonists such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). Formyl peptide receptor (FPR) and formyl peptide receptor-like 1 (FPRL1), a superfamily of seven transmembrane (TM) proteins, are expressed on human neutrophils as the fMLP binding receptors. We found that human neutrophils pretreated with human formyl peptide receptor transmembrane (hFPRTM) peptides were enhanced superoxide anion production when stimulated with fMLP. However, a membrane protein interacting with hFPRTM peptides is not identified. To explore the sequence dependences of the TM peptides for neutrophil proming activities, peptides possess the TM sequences of formyl peptide receptor (FPR), FPR like 1 receptor (FPRL1), and GABA receptor were synthesized by solid-phase method with Fmoc chemistry. Homogeneities and structures of synthetic peptides were confirmed by HPLC and MALDI-TOF MS. The biological activities of synthetic peptides were carried out as superoxide production for human neutrophils. Neutrophils treated with TM peptides from FPR and FPRL1 produced 2-3 folds of superoxide anion by the treatment of fMLP, neutrophil agonist. TM peptide from GABA receptor exhibited no significant priming activity. These results suggested the priming effect of TM peptide for neutrophil was sequence dependence and it required the FPR related sequences.
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