| Project/Area Number |
11557176
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
SAITO Shin-ya Grad.School Pharm.Sci., Tohoku University, Res.Instructor, 大学院・薬学研究科, 助手 (80271849)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNAGA Kimihiro Grad.School Pharm.Sci., Tohoku University, Res.Instructor, 大学院・薬学研究科, 助手 (90222306)
NAKAHATA Norimichi Grad.School Pharm.Sci., Tohoku University, Professor, 大学院・薬学研究科, 教授 (60045804)
OHIZUMI Yasushi Grad.School Pharm.Sci., Tohoku University, Professor, 大学院・薬学研究科, 教授 (00006355)
ISHIDA Yukisato Mitsubishi Kasei Institute of Life Science, Senior Researcher, 生命研, 主任研究員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | myosin / actin / troponin / tropomyosin / superprecipitation / skeletal muscle / 生理活性物質 / goniodomin A / 心筋 / 骨格筋 |
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| Research Abstract |
Hypertrophic cardiomyopathy is relating to mutation in myosin, tropomyosin or troponin in cardiac muscle. The mutant myosin looses its susceptibility to actin activation of its ATPase activity. Therefore, the compounds that directly affect on cardiac muscle specific contractile proteins are extremely attractive to develop new type of medicinal for cardiomyopathy. Only in striated muscle, one may find that troponin bind to and regulating interaction of actin with myosin. This is because, differing from other smooth muscle or non-muscle cells, the myosin of striated muscle type is always in active state. Namely, in striated muscle, troponin/tropomyosin directly regulating the interaction of actomyosin, whereas various proteins are intermediating to regulate the interaction in smooth or non-muscle cells. Therefore, the compounds that directly affecting on striated muscle myosin or troponin can possess strong tissue selectivity. We found that thiotetromycin, isolated from Streptomyces sp. facilitated superprecipitation of myosin B.Superprecipitation is a model reaction of muscle contraction, this result suggesting that thiotetromycin facilitating the interaction of actomyosin. We further found that thiotetromycin inhibits actomyosin ATPase activity by directly affecting on actin. However, in the presence of troponin/tropomyosin, thiotetromycin do not show any inhibitoly effect. The mechanism of activating superprecipitation is still not clear, this compound is extremely interesting as interaction activator. We also found that goniodomin A isolated from dinoflagera, facilitates superprecipitation of myosin B.On the other hand, goniodomin A inhibited Ca-induced contraction in skinned fiber in concentration dependent manner. Goniodomin A also revealed facilitating effect on actomyosin ATPase activity although this effect attenuated by excessive concentration of troponin/tropomyosin. We found that amphidinolide B can also facilitate the activity of actomyosin ATPase.
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