1998 Fiscal Year Final Research Report Summary
Mechanism of apoptosis and DNA methylation during development and aging of neuronal cells
| Project/Area Number |
09660314
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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 |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAYAMA Hiroyuki The University of Tokyo, Graduate School of agricultural and life sciences, Associate professor, 大学院・農学生命科学研究科, 助教授 (40155891)
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| Co-Investigator(Kenkyū-buntansha) |
UETSUKA Koji The University of Tokyo, Graduate School of agricultural and life sciences, Asso, 大学院・農学生命科学研究科, 助手 (60251419)
NISHIHARA Masugi The University of Tokyo, Graduate School of agricultural and life sciences, Asso, 大学院・農学生命科学研究科, 助教授 (90145673)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Apoptosis / 5-Azacytidine / PC12 cells / Ribosomal protein L4 (rpL4) / DNA methylation / Aging / Development / Dementia |
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| Research Abstract |
5-Azacytidine (5AzC) is a cytidine analogue and the number 5 carbon atom of the pyrimidine ring is replaced by a nitrogen atom. Intake of 5AzC into the prymidine ring may render the 5 position unable to be methylated, leading activation of a certain gene with demethylated promotor region. An unknown apoptosis-related protein(s) newly produced would be involved in the 5AzC-induced apoptosis. The present study is performed to isolate such apoptosis-related gene(s)/protein(s) and to clarify the mechanism through which the gene(s) would be activated.
The results clarified that 5AzC-induced apoptosis in the neuronal tissue or cells is closely involved in DNA demethylation. In addition, the increased expression of ribosomal protein L4 (rpL4) gene was demonstrated before apoptosis in PC12 cells (originated from rat pheochromocytoma) treated with 5AzC.Furthermore, apoptosis was also induced in cells transfected with rpL4 gene. Therefore, it was revealed that the expression of rpL4 gene is an crucial event for neuronal apoptosis.
Recently, the life span of companion animals such as dogs and cats is expanded. As the life span elongates, more aged dogs suffer from dementia-like condition. We demonstrated that the number of apoptotic brain cells were closely related to progression of the dementia-like condition. In the present study, we also tried to reveal the relation between apoptosis-related genes and dementia in the brain of aged dogs. Not enough results are obtained until the present and further studies will clarify the relations.
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Research Products
(20 results)
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[Publications] Nakamura, S., Tamaoka, A., Sawamura, N., Kiatipattanasakul, W., Nakayama, H., Shoji, S., Yoshikawa, Y., and Doi, K.: "Deposition of amyloid β protein(A β)subtypes(A β 40 and A β 42(43))in canine senile plaques and cerebral amyloid angiopathy." Acta Neuropathol.94. 323-328 (1997)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kuroki, K., Uchida, K., Kiatipattanasakul, W., Nakamura, S., Yamaguchi, R., Nakayama, H., Doi, K., and Tateyama, S: "Immunohistochemical detection of tau protein in various nonhuman animal brains." Neuropathol.17. 174-180 (1997)
Description
「研究成果報告書概要(和文)」より
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[Publications] Lu, D.-P., Nakayama, H., Shinozuka, J., Uetsuka, K., Taki, R., and Doi, K.: "5-Azacytidine-induced apoptosis in the central nervous system of developing rat fetuses." J.Toxicol.Pathol.11. 133-136 (1998)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kajikawa, S., Nakayama, H., Suzuki, M., Takashima, A., Murayama, O., Nishihara, M., Takahashi, M., and Doi, K.: "Increased expression of rat ribosomal protein L4 mRNA in 5-azacytidine-treated PC12 cells prior to apoptosis." Biochem.Biophys.Res.Commun.252. 220-240 (1998)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ishigami, N., Shinozuka, J., Katayama, K., Uetsuka, K., Nakayama, H.and Doi, K.: "Apoptosis in the developing mouse embryos from T-2 toxin-inoculated dams." Histol.Histopathol.(in press).
Description
「研究成果報告書概要(和文)」より
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[Publications] Hossain, M,M., Nakayama, H., Takashima, A., Goto, N., and Doi, K.: "5-azacytidine (5Az) induces apoptosis in PC12 cells : A model for 5Az-induced developing neuronal cell apoptosis." Histol.Histopathol.12 :. 439-455 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakamura, S., Tamaoka, A., Sawamura, N., Kiatioattanasakul, W., Nakayama, H., Shoji, S., Yoshikawa, Y., and Doi, K.: "Deposition of amyloid beta protein (A beta) subtypes (A beta 40 and A beta 42 (43) in canine senile plaques and cerebral amyloid angiopathy." Acta Neuropathol.94 :. 323-328 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kuroki, K., Uchida, K., Kiatioattanasakul, W., Nakamura, S., Yamaguchi, R., Nakayama, H., Doi, K., and Tateyama, S.: "Immunohistochemical detection of tau protein in various nonhuman animal brains." Neuropathol.95 :. 174-180 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Lu, D.-P., Nakayama, H., Shinozaki, J., Uetsuka, K., Taki, R., and Doi, K.: "5-azacytidine-induced apoptosis in the central nervous system of developing rat fetuses." J.Toxicol.Pathol.11 :. 133-136 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kajikawa, S., Nakayama, H., Suzuki, M., Takashima, A., Murayama, O., Nishihara, M., Takahashi, M., and Doi, K.: "Increased expression of rat ribosomal protein L4 mRNA in 5-azacytidine-treated PC12 cells prior to apoptosis." Biochem.Biophys.Res.Commun.252 :. 220-224 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ishigami, N., Shinozaki, J., Katayama, K., Uetsuka, K., Nakayama, H.and Doi, K.: "Apoptosis in the developing mouse embryos from T-2 toxin-inoculated dams." Histol.Histopathol.(in press).
Description
「研究成果報告書概要(欧文)」より
