2022 Fiscal Year Final Research Report
Initiation mechanisms of apoptosis for elimination of oxiditively damaged RNA
Project/Area Number |
20K06495
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43010:Molecular biology-related
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Research Institution | Kamakura Women's University (2021-2022) Fukuoka Dental College (2020) |
Principal Investigator |
Ishii Takashi 鎌倉女子大学, 家政学部, 准教授 (70516731)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 酸化ストレス / 酸化損傷 / 8-oxoG / RNA / アポトーシス / 老化 / 神経変性疾患 |
Outline of Final Research Achievements |
Oxidative stress induces loss of homeostasis through the oxidation of various types of biomolecules. As a result, aging and neurodegenerative diseases are thought to occur. In our study, we searched for factors involved in elimination of oxidized RNA. Oxidatively damaged RNA causes abnormalities in the transduction of genetic information, which causes disruption of cell homeostasis. Research results revealed that two proteins, PCBP1 and PCBP2, act in the mechanism of apoptotic elimination of cells that have produced oxidatively damaged RNA. In addition, as evidence to support this, it has been revealed that the expression level of PCBP2 is downregulated in brain neurons of patients who develop neurodegenerative diseases.
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Free Research Field |
分子生物学
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Academic Significance and Societal Importance of the Research Achievements |
酸化損傷塩基8-oxoGが生じると遺伝情報の正確な伝達が行われなくなる。その結果、DNAの変異による遺伝子疾患(がん等)や、RNAの変異による異常タンパク質合成が引き金となる老化や神経変性疾患(アルツハイマー病や認知症等)が誘導される。この危機を回避するために、生物は様々な機構を使って8-oxoGを排除している。その1つとして、我々はPCBP1とPCBP2による酸化損傷RNA排除機構の存在を明らかにした。この機構は、重度の酸化損傷を受けたRNAを持つ細胞をアポトーシスにより排除することで生体の恒常性維持に働くと考えられる。
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