Project/Area Number |
06045035
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Research Category |
Grant-in-Aid for international Scientific Research
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Allocation Type | Single-year Grants |
Section | University-to-University Cooperative Research |
Research Institution | Kagawa Medical University |
Principal Investigator |
IRINO Shozo Kagawa Medical University・President, 学長 (50033056)
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Co-Investigator(Kenkyū-buntansha) |
WAISMAN David M University of Calgary・Professor, 医学部, 教授
TAMAOKI Taiki University of Calgary・Professor, 医学部, 教授
SMITH Eldon カルガリ大学, 医学部長
YAMAGUCHI Fuminori Kagawa Medical University・Research Associate, 医学部, 助手 (40271085)
TOKUDA Masaaki Kagawa Medical University・Associate Professor, 医学部, 助教授 (10163974)
TAKAHARA Jiro Kagawa Medical University・Professor, 医学部, 教授 (00033085)
TAKEUCHI Yoshiki Kagawa Medical University・Professor, 医学部, 教授 (20116619)
HATASE Osamu Kagawa Medical University・Professor, 医学部, 教授 (50033220)
HOSOKAWA Kiyoshi Kagawa Medical University・Vice President, 副学長 (70093698)
ELDON Smith University of Calgary・Dean
細見 弘 香川医科大学, 医学部, 教授 (70030864)
WANG Jerry H カルガリ大学, 医学部, 教授
村上 哲英 香川医科大学, 医学部, 教授 (20032873)
宇多 弘次 香川医科大学, 副学長 (80107044)
|
Project Period (FY) |
1994 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | Cdk5 / p35 / calcineurin / Ca / Calmodulin kinases / calcium / Lymphocyte / Cartilage / Brain / Retina / Cyclin-dependent kinase 5 / アルツハイマー病 / calmodulin kinase-IV / リン酸化 / 細胞内情報伝達 / クロストーク / パーキンソン病 / カルモジュリンキナーゼIV / 白血病細胞 / Cdk 5 / アルツハイマー脳 / MARCKS / カルモジュリン依存性リン酸化酵素IV |
Research Abstract |
In the nervous system, we found the novel regulatory factor p35 which is related to cyclins and controls cyclin-dependent kinase 5 (Cdk5). In the Alzheimer is brain, both Cdk 5 and p35 were shown to in crease in amount. We also demonstrated that Tau protein could cause the tangle formation observed in the senile plaques of Alzheimer is deisease by phosphorylating Cdk5/p35. The distribution of Cdk5 and p35 in the nervous system was examined, and both were shown to exist in Purkinje cells but not in granular cells. Both were present in retina, especially in the inner nuclear layr and ganglion cells. p39, an isoform of p35, was also present in retina. In the normal white blood cells (WBC) and leukemic WBC,cross-talk mechanisms were compared. Especially, the phosphorylation level of the intrinsic proteins was much higher in the leukemic WBC than the normal WBC.We showed the intracellular calcium level was 20-30% higher in leukemic WBC than normal WBC,and the amount of calcium/calmodulin-dependent protein kinase IV (CaMK-IV) was increased also in leukemic WBC. CaMK-IV was shown to be expressed during the initial atages of the chondrogenesis, especially in the proliferating zone, but not in the later stages. This indicates that CaMK-IV is actively involved in the chodrogenesis during the initial differentiation of immature chondrocytes. The substrate proteins have been analyzed. The simultaneous analysis of CaMK-I,-II and IV and calcineurin (CaN), a calcium/calmodulin-dependent phosphatase, was performed in the rat hippocampus. We successfully demonstrated that CaMK-I and -IV as well as already reported CaMK-II and CaN were expressed in the hippocampus. The change in the amount of these enzymes in the Alzheimer is brain has been analysing.
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