Elucidation of physiological regulatory mechanisms by a novel family of neutrophil-activating peptides derived from mitochondrial proteins
| Project/Area Number |
16K01923
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Nagahama Institute of Bio-Science and Technology |
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Principal Investigator |
Mukai Hidehito 長浜バイオ大学, バイオサイエンス学部, 准教授 (20251027)
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| Research Collaborator |
HATTORI Tatsuya
MARUTANI Takayuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 生体機能物質 / 活性発現の分子機構 / クリプタイド / 自然免疫機構 / 炎症 / 好中球 / 肝傷害モデル / エンドトキシン / 肥満細胞 |
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| Outline of Final Research Achievements |
Recently we isolated and identified a novel family of neutrophil-activating peptides, mitocryptides (MCTs), derived from various mitochondrial proteins including mitocryptide-1 (MCT-1) and mitocryptide-2 (MCT-2). Here we showed that the administration of MCTs into mouse peritoneal cavity induced dramatic neutrophil infiltration at limited concentrations. We also demonstrated that intravenous pre-injection of neutralizing antibodies against MCTs suppressed neutrophil infiltration and tissue injury in the mouse hepatic injury model caused by acetaminophen, indicating that MCTs involve the inflammation mechanisms in injury tissues.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、ミトコンドリアタンパク質由来の一群の新規好中球活性化ペプチド、「マイトクリプタイド」（MCTs）を同定しているが、それらペプチドの生体における存在意義や病態との関連は明らかとなっていない。そこで本研究では、これらMCTsの生体における役割を解明するための検討を行った。その結果、マウスにおいて実験的に誘導した肝傷害モデルにおいて、MCTsがその増悪に関わっていることを、それらに対する中和抗体を用いることで、世界で初めて示すことに成功した。この研究成果は、多臓器不全や虚血傷害といった未だ有効な治療法が確立されていない炎症性疾病の治療に道を開く画期的成果であると考えられる。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Mitochondrial protein-derived cryptides: are endogenous N-formylated peptides including mitocryptide-2 components of mitochondrial damage-associated molecular patterns?2016
Author(s)
Marutani, T., Hattori, T., Tsutsumi, K., Koike, Y., Harada, A., Noguchi, K., Kiso, Y., and Mukai, H.
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Journal Title
Biopolymers: Peptide Science
Volume: 106
Issue: 4
Pages: 580-587
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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