| Project/Area Number |
17K08669
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Juntendo University |
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Principal Investigator |
Nishida Yuya 順天堂大学, 医学部, 准教授 (10581449)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アシル化 / ケトン体 / ヒストン修飾 / アセチル化 / βヒドロキシブチル化 / ケトジェニック食 / βヒドロキシ酪酸化 / ケトン食 / βハイドロキシ酪酸 / ヒストンアシル化 |
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| Outline of Final Research Achievements |
It has been reported that protein lysine acylations, including acetylation and beta-hydroxybutyrylation, are closely related to ketone body metabolism. In this study, we investigated whether those lysine modifications are induced after mice were fed with ketogenic diet, containing no carbohydrate. The mice manifested increase of lysine acetylation and beta-hydroxybutyrylation in whole cell lysates of various organs such as live, heart and kidney. However, the amounts of those modifications in histones are not always proportional to those in whole cell lysates, suggesting that lysine acylations are regulated by different mechanisms between organelles. In addition, we developed the system in which genome-wide gRNA screening is feasible using CRISPR/Cas9 system, focusing on identifying regulators for autophagic flux, in order to examine key molecules involved in protein acylation or de-acylation.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化が進む我が国において健康寿命の延長は喫緊の課題であり、ケトジェニック食の有効性が示唆されているが、そのメカニズムの一端には本研究で明らかにしたタンパクのアシル化修飾の制御が関係しているものと考えられる。その分子機構を明らかにすることにより、健康長寿に寄与する新しい治療法の開発につながることが期待され、本研究で確立したCRISPR/Cas9によるゲノムワイドスクリーニング法はその分子メカニズムの解明に大きく貢献すると考えられる。
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