Elucidation of physiological significance of a novel regulator of neuronal functions and its application to functional regeneration of brain
| Project/Area Number |
16590041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAKUNI Tohru Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (30333793)
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| Co-Investigator(Kenkyū-buntansha) |
OHIZUMI Yasushi Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00006355)
NAKAJIMA Akira Tohoku University, Graduate School of Pharmaceutical Sciences, Instructor, 大学院・薬学研究科, 助手 (20419237)
SAITO Shin-ya Tohoku University, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (80271849)
李 玉山 東北大学, 大学院・薬学研究科, 教務職員 (50344685)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | V-1 / CapZ / Actin dynamics / Transcriptional regulation / TH gene / Neurogenesis / Regeneratin of brain function / CNS neurodegeneration / レトロウイルスベクター / アクチンフィラメント形成 / 神経機能制御 / 神経再生 / 脳神経幹細胞 / 天然ハーブエキス / 蛋白質相互作用 / neurosphere |
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| Research Abstract |
V-1 has been identified as a novel ankyrin repeat protein which exhibits a transient increase in the protein expression level during the postnatal brain development. This protein also has the activity to control both tyrosine hydroxylase (TH) gene expression and catecholamine release in PC12D cells, and associates with CapZ, an actin capping protein to regulate actin polymerization in vitro. However the physiological significance of V-1 in controlling actin dynamics remains unknown. In this study, we for the first time showed that in V-1-overexpressing PC12D transfectant, the amount of CapZ in the cytoskeletal fraction was decreased, whereas that in the cytoplasmic fraction was increased, as compared with of vector control transfectant. The amount of CapZ-associated actin filaments was also decreased to produce an increment of the ratio of F-/G-actin in V-1 transfectant. Moreover the capping activity of CapZ was stimulated at 5 min after treatment with forskolin, accompanied by its translocation from the cytoplasmic to cytoskeletal fractions in PC12D cells. It is thus suggested that V-1 serves as a novel cytoplasmic anchor of CapZ and that control of CapZ activity by its interaction with V-1 probably acts as a novel PKA-dependent regulatory mechanism of actin dynamics in vivo. Furthermore, as the first step to searching for natural products with the activity to positively or negatively control the interaction between V-1 and CapZ in vivo, we screened twenty natural herbal extracts to examine whether these herbs affected the interaction between V-1 and CapZ. Consequently several herbs showed such a pharmacological actin.
Also we constructed a retrovirus vector for expression of V-1 to successfully overexpress its protein in neural stem cells. Notably overexpression of V-1 in neural stem cells appreciably produced astrocytes and neurons in the growth medium. In addition the V-1 retrovirus inhibited differentiation of a preadipocyte cell line to adipocytes.
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Report
(3 results)
Research Products
(38 results)
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[Journal Article] Garcinone B reduces prostaglandin E_2 release and NF-κB-mediated transcription in C_6 cells.2006
Author(s)
Yamakuni, T., Aoki, K., Nakatani, K., Kondo, N., Oku, H., Ishiguro, K., Ohizumi, Y.
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Journal Title
Neurosci.Lett. 394
Pages: 206-210
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats2006
Author(s)
Matsuzaki, K., Yamakuni, T., Hashimoto, M., Haque, A.M., Shido, O., Mimaki, Y., Sashida, Y., Ohizumi, Y.
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Journal Title
Neurosci.Lett. 400
Pages: 230-234
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intracellular cAMP controls a physical association of V-1 with Cap Z in cultured mammalian endocrine cells.2005
Author(s)
Kitazawa, M., Yamakuni, T., Song, S.-Y., Kato, C., Tsuchiya, R., Ishida, M., Suzuki, N., Adachi, E., Iwashita, S., Ueno, S., Yanagihara, N., Taoka, M., Isobe, T., Ohizumi, Y.
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Journal Title
Biochem.Biophys.Res.Commun. 331
Pages: 181-186
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanism of neurotropic action of nobiletin in PC12D cells.2005
Author(s)
Nagase, H., Yamakuni, T., Matsuzaki, K., Maruyama, Y., Kasahara, J., Fukunaga, K., Hinohara, Y., Kondo, S., Mimaki, Y., Sashida, Y., Tank, A.W., Ohizumi, Y.
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Journal Title
Biochemistry 44
Pages: 13683-13691
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nobiletin and its related flavonoids with CRE-dependent transcription- stimulating and neuritegenic activities.2005
Author(s)
Nagase, H., Omae, N., Omori, A., Nakagawasai, O., Tadano, T., Yokosuka, A., Sashida, Y., Mimaki, Y., Yamakuni, T., Ohizumi, Y.
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Journal Title
Biochem.Biophys.Res.Commun. 377
Pages: 1330-1336
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] _Y-Mangostin inhibits inhibitor-κB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells.2004
Author(s)
Nakatani, K., Yamakuni, T., Kondo, N., Arakawa, T., Oosawa, K., Shimura, S., Ohizumi, Y.
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Journal Title
Mol.Pharmacol. 66
Pages: 667-674
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IC101 induces apotosis by Akt dephosphorylation via an inhibition of heat shock protein 90-ATP binding activity accompanied by preventing the interaction with Akt in L1210 cells.2004
Author(s)
Fujiwara, H., Yamakuni, T., Ueno, M., Ishizuka, M., Shinkawa, T., Isobe, T., Ohizumi, Y.
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Journal Title
J.Pharmacol.Exp.Ther. 310
Pages: 1288-1295
Description
「研究成果報告書概要(欧文)」より
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