1995 Fiscal Year Final Research Report Summary
Development of new drug therapy for atherosclerosis
| Project/Area Number |
06557058
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka University |
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Principal Investigator |
KAWATA Sumio Osaka Univ.Med.Sch., Associate Professor, 医学部, 助教授 (90183285)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Hirofumi Kyowa Hakko, Tokyo Institute, Chief Administrator, 東京研究所, 管理室長
TAMURA Shinji Osaka Univ.Med.Sch., Assistant, 医学部, 助手 (30243223)
YAMASHITA Shizuya Osaka Univ.Med.Sch., Assistant, 医学部, 助手 (60243242)
TAKEMURA Kaoru Osaka Univ.Med.Sch., Assistant Professor, 医学部, 講師 (00161240)
MATSUZAWA Yuji Osaka Univ.Med.Sch., Professor, 医学部, 教授 (70116101)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Atherosclerosis / Vascular smooth muscle cells / Ras p21 / Farnesyl ; protein transferase / manumycin |
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| Research Abstract |
Migration and proliferation of vascular smooth muscle cells (VSMC) play important roles in development of atherosclerosis. The migration and proliferation of VSMC are known to be stimulated by growth factors. Ras p21 is a key component in intracellular signal transduction pathway for cell growth via growth factor receptors.
Farnesylation of C-terminal of Ras p21 is required for its function as signal transducer. This farnesylation Ras p21 is catalyzed by farnesyl : protein transferase.
In this project, we examined inhibitory effects of manumycin, a potent farnesyl : protein transferase inhibitor, on VSMC growth in vitro and in vivo. Manumycin inhibited VSMC proliferation in vitro. Then, we administered manumycin to rats with balloon injury in carotid arteries. As a result, this inhibitor significantly suppressed intimal thickening in injured carotid arteries.
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