| Project/Area Number |
26505012
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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 |
オミクス計測科学
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| Research Institution | Mukogawa Women's University |
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Principal Investigator |
Okada Yasuyo 武庫川女子大学, 薬学部, 講師 (70211117)
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| Co-Investigator(Kenkyū-buntansha) |
市川 厚 武庫川女子大学, 薬学部, 教授 (10025695)
入江 徹美 熊本大学, 大学院生命科学研究部(薬), 教授 (60150546)
竹山 志朱代 (堀山 / 竹山 志朱代(堀山志朱代)) 武庫川女子大学, バイオサイエンス研究所, 助教 (80411982)
西川 淳一 武庫川女子大学, 薬学部, 教授 (90218131)
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| Co-Investigator(Renkei-kenkyūsha) |
BAMBA takeshi 九州大学, 生体防御医学研究所, 教授 (10432444)
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| Research Collaborator |
UEDA erika
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ニーマンピックＣ型病 / マルトシル－βシクロデキストリン / コレステロール / リソゾーム / LC/MS / ニーマン一ピック病Ｃ型 / ニーマンピック病Ｃ型 / マルトシル‐βシクロデキストリン |
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| Outline of Final Research Achievements |
Niemann-Pick Type C (NPC) disease is a lysosomal storage disease characterized by excess accumulation of unesterified cholesterol in the lysosomes. β-cyclodextrin derivatives (βCDs) form inclusion complexes with unesterified cholesterol and are a subject of intense research in the context of treating the NPC disease. In this study, we used quantitative LC/MS/MS to demonstrate that a 6-O-α-maltosyl-β-cyclodextrin derivative (Mal-βCD) is internalized by Npc1 KO and CHO-JP17 cells by fluid-phase endocytosis. This is followed by Mal-βCD transport to the lysosomes, where the majority of Mal-βCD is metabolized to Glc-βCD. Finally, the lysosomal βCDs and unesterified cholesterol are released to the extracellular fluid. We believe that our study makes a significant contribution to the literature because it not only provides insight into the intracellular fate of internalized Mal-βCD but also may inform future treatment of the NPC disease.
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