2001 Fiscal Year Final Research Report Summary
Effect of Prnp gene to prion protein expression
| Project/Area Number |
12460131
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
ONODERA Takashi Graduate School of Agriculture and Life Sciences, THE UNIVERSITY OF TOKYO, Professor, 大学院・農学生命科学研究科, 教授 (90012781)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Keiichi Graduate School of Agriculture and Life Sciences, THE UNIVERSITY OF TOKYO, Assist. Professor, 大学院・農学生命科学研究科, 助手 (10311630)
MATSUMOTO Yoshitsugu Graduate School of Agriculture and Life Sciences, THE UNIVERSITY OF TOKYO, Assoc. Professor, 大学院・農学生命科学研究科, 助教授 (00173922)
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| Project Period (FY) |
2000 – 2001
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| Keywords | prion / prion protein / serapie / Cu / Zn SOD / mouse / Doppel / gene tageting / neural degeneration |
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| Research Abstract |
Some of the authors previously demonstrated the relation between cellular prion protein (PrP^c) and apoptosis using immortalized prion protein gene (Prnp)-deficient neuronal cells. However, the mechanism(s) by which PrP^c prevents apoptosis remains unclear. In this study, the authors analyzed apoptosis of Prnp^<-/-> cells using gene transfer of apoptosis-related genes. Transfection of Prnp^<-/-> cells with bcl-2, bcl-x_L or SOD-1, which encodes Cu/Zn superoxide dismutase (SOD), inhibited apoptosis induced by serum deprivation. As serum deprivation decreased Bcl-2 and Bcl-x_L proteins in-Prnp^<-/-> cells, these cells are thought to die via apoptosis pathways regulated by the Bcl-2 family and intracellular superoxides. Re-introduction of Prnp upregulated SOD activity and eliminated superoxide anion generation without inducing changes hi Bcl-2, Bcl-x_L and Cu/Zn SOD expression levels. As PrP^c was bound to copper in the octapeptide repeats, these results suggested that PrP^c inhibited apoptosis by upregulation of SOD activity due to copper metabolism regulation.
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