| Project/Area Number |
16K08496
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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 |
General physiology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KISHI Hiroko 山口大学, 大学院医学系研究科, 准教授 (40359899)
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| Co-Investigator(Kenkyū-buntansha) |
張 影 山口大学, 大学院医学系研究科, 講師 (10711260)
森田 知佳 山口大学, 大学院医学系研究科, 助教 (70763796)
小林 誠 山口大学, 大学院医学系研究科, 教授 (80225515)
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| Research Collaborator |
LYU Bochao
ZHANG Min
LU Qian
LI Nan
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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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 血管平滑筋 / 異常収縮 / 細胞骨格 / カルパイン / 血管異常収縮 / 機能プロテオミクス / 生理学 |
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| Outline of Final Research Achievements |
Whereas normal vascular contraction which regulates normal blood pressure is cytosolic Ca2+-dependent, abnormal vascular contraction which plays a critical role in the pathophysiology of sudden and fatal ischemic diseases such as myocardial infarction and post-SAH cerebral vasospasm, is Ca2+-independent, that is, it does not require cytosolic Ca2+ elevation. In this research project, we attempted to clarify the involvement of calpain and cytoskeletal proteins in the signal transduction of abnormal vascular smooth muscle contraction. We found that sphingosylphosphorylcholine (SPC) induced calpain activation as well as abnormal contraction in vascular smooth muscle. We also revealed the cleavage site of V1 by calpain using mass spectrometry. Furthermore, we found a calpain inhibitor inhibited abnormal vascular contraction without affecting normal vascular contraction.
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義：血管異常収縮のシグナル伝達機構は正常収縮と異なりカルシウム非依存性であるが詳細は不明であった。本研究は血管異常収縮シグナル伝達において新規の機構を解明したものである。
社会的意義：血管異常収縮が引き起こす心筋梗塞やくも膜下出血後脳血管攣縮はしばしば難治性である。本研究はこれらの疾患の特効薬開発のための新規のターゲットとしてカルパインおよび細胞骨格V1を示唆するものである。
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