| Project/Area Number |
09680766
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
YAMAMOTO Hideyuki Kumamoto University School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Jiro Kumamoto University School of Medicine, Pharmacology, Instructor, 医学部, 助手 (10295131)
FUKUNAGA Kohji Kumamoto University School of Medicine, Pharmacology, Assoicate Professor, 医学部, 助教授 (90136721)
MIYAMOTO Eishichi Kumamoto University School of Medicine, Pharmacology, Professor, 医学部, 教授 (50109659)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Brain-derived neurotrophic factor (BDNF) / Ca^<2+> / calmodulin-dependent protein kinase II / Cytoskeletal proteins / Hippocampus / Naurite outgrowth / NG108-15 cells / Nuclear localization signal / Temporal lobe epilepsy / カルモデュリン / 転写調節 / 脳由来神経栄養因子(BDNF) / アルツハイマー病 / CaMキナーゼII / Cキナーゼ / MARCKS / 燐酸化特異抗体 |
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| Research Abstract |
A morphological characteristic of temporal lobe epilepsy consists of the abnormal neurite outgrowth of the hippocampal dentate granule cells. Some isoforms of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) may be related to this abnormal neurite outgrowth. Among CaM kinase II, four subunits and several isoforms have been identified from brain. In order to investigate the pathophysiological roles of each isoform of CaM kinase II in temporal lobe epilepsy, we studied about the structures and functions of CaM kinase II isoforms mainly about the delta subunit of CaM kinase II (CaM kinase IIdelta). 1) We prepared the antibody against CaM kinase IIdelta and examined the localization of the subunit in brain. 2) We obtained the cDNAs of 6 isoforms of CaM kinase IIdelta from rat brain. Among these isoforms, delta3 was localized in the nuclei in transfected NG1O8-15 cells. 3) Overexpression of delta3 in NG1O8- 15 cells induced the gene expression of brain-derived neurotrophic factor (BDNF) which promotes survival and differentiation of specific populations of neurons in the brain. 4) We found that the major isoform of CaM kinase II in PC12 cells and NG108-15 cells was delta2. And delta2 appeared to be mainly localized in Golgi's apparatus.
5) Other isoforms were localized in the cytoplasm in NG 108-15 cells. Therefore, these isoforms may be involved in the regulation of neurite outgrowth via phosphorylation of cytoskeletal proteins such as microtubule-associated protein 2.
These results suggest that each isoform is localized in the specific site in neurons to play some important roles in neuronal functions.
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