Project/Area Number |
11557022
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
寄生虫学(含医用動物学)
|
Research Institution | Mie University |
Principal Investigator |
CHINZEI Yasuo Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60024709)
|
Co-Investigator(Kenkyū-buntansha) |
ITO Masaaki Mie University, Hospital, Assistant Professor, 医学部附属病院, 講師 (00223181)
YUDA Masao Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (90293779)
MIURA Ken Mie University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60219582)
|
Project Period (FY) |
1999 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥6,600,000 (Direct Cost: ¥6,600,000)
|
Keywords | blood sucking insect / salivary gland / bio-active molecules / anticoagulant / anti-inflammation drug / 創薬 / 吸血性昆虫 / 吸血性ダニ / 生理活性物質 / 血液凝固因子 / 抗血液凝固物質 / 接触相 / 血液凝固系 / 第9因子 / オオサシガメ / プロリキシンS / 血液凝固 / インヒビター / ファクターIX / プロリクシンS |
Research Abstract |
The salivary glands of blood sucking insects contain some bio-active substances to control blood coagulation and blood vessel of host animals for assisting a continuous blood feeding. In this study, we searched these bio-active molecules from the glands and analyzed the molecular structure, activity and mode of action to elucidate the biological significance of these molecules, and tried to develop a material for novel medicine. We used two blood sucking insects, Triatoma infestans (Ti) and Anopheles stephensi (As), and the tick, Haemaphisalis bispinosa (Hb) as material animals. We established the data bases of salivary gland EST of these animals, and analyzed 179, 120 and 218 molecules with novel sequences, respectively. We identified 5, 3, and 3 novel bio-active molecules respectively after expression by baculo virus expression system and analysis of activities. 'Hamadarin', one of them is isolated and identified from the salivary glands of anopheline mosquito As. We found hamadalin inhibits factor XII of coagulation cascade and high molecular weight kininogen by binding them to the binding sites of these molecules to negative charged surface, and as results inhibits coagulation cascade and generation of bladikinin and therefore inflammation. Hamadalin has a possibility to be a lead molecules developing novel anticoagulant and anti-inflammation drug.
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