| Project/Area Number |
18K14881
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | サイクリックADPリボース / ニコチンアミドアデニンジヌクレオチド / 安定同位体 / 定量系 / ターゲットメタボロミクス / 重水素化 / 有機合成 / LC-MS |
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| Outline of Final Research Achievements |
Cyclic ADP ribose (cADPR) is the nicotinamide adenine dinucleotide (NAD) major metabolite. cADPR is an important messenger molecule that has been pointed out to be involved in various life phenomena. For example, oxytocin release, insulin secretion, inflammatory response, and even stem cell self-renewal. In this study, we focused on intracellular cADPR, which could not be quantified due to the extremely small amount in the previous metabolome studies, and constructed a highly sensitive and accurate quantification method for cADPR using LC / MS. A stable isotope of cADPR was synthesized as an internal standard and a quantitative system of cADPR was constructed. Sensitivity was increased 1,000 times more than previously reported, and sufficient sensitivity was achieved to quantify intracellular cADPR.
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| Academic Significance and Societal Importance of the Research Achievements |
cADPRは、これまでのメタボローム研究において極微量であるために定量できていなかったが、本研究課題によって、既報より 1,000 倍以上感度が上昇した。細胞内 cADPR を定量するに十分な感度を達成し、cADPR研究に新たな評価系を提案することができた。
本系はNADを同時に定量可能であり、NAD メタボロミクスや種々の疾患機序、および薬の詳細な作用機序解明に応用できる可能性がある。今後は本cADPR定量法をベースとしたNAD関連代謝物質の一斉定量法に展開する予定である。
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