| Project/Area Number |
17K16981
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 白内障病態形成 / 計算化学 / NMR / 白内障の病態形成 / アスパラギン酸残基異性化 / アミノ酸残基の非酵素反応 / 紫外線の影響 / 乳酸触媒 / リン酸触媒 / 計算化学と生化学実験 / 眼科学 / 眼病理学 / 白内障 |
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| Outline of Final Research Achievements |
The non-enzymatic reactions of aspartic acid and asparagine residues in crystallin, which are involved in the pathogenesis of cataracts, require a catalyst. Based on the hypothesis that lactate, phosphate, and oxidized residues act as catalysts for this reaction, we conducted a study using computational chemistry, physicochemical experiments, and biochemical experiments.
In the computational chemistry study, the lactate-catalyzed activation barrier was near the value at which the reaction proceeds under physiological conditions. This was supported by biochemical experiments. Furthermore, the effect of buffer solution was also confirmed. The effect of UV light was clarified by analyzing the changes in the NMR spectra of the UV-irradiated samples and the structural changes of amino acids.
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| Academic Significance and Societal Importance of the Research Achievements |
白内障の原因は様々考えられるが、その1つとしてクリスタリン中のアスパラギン酸（Asp）残基の異性化が挙げられる。Asp残基が異性化する経路は非酵素反応だが、反応には触媒が必要となる。本研究では、乳酸やリン酸緩衝液を異性化経路の触媒とし、反応が生理的条件で起こるかを計算化学的に明らかとし、その結果を生化学実験により補完確認すること。また、紫外線の影響をNMR法を用いてAsp残基の異性化から明らかとする方法を確立すること。以上から、世界の失明原因第1位である白内障の病態形成に関わる因子解明とその新規検出方法の検討を行った。
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