| Project/Area Number |
17K00892
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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 |
Eating habits
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| Research Institution | Chubu University |
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Principal Investigator |
LU Rui 中部大学, 応用生物学部, 講師 (80381862)
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| Co-Investigator(Kenkyū-buntansha) |
横山 信治 中部大学, 生物機能開発研究所, 客員教授 (10142192)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HDL / ABCA1 / HDL代謝 / 高血糖 / AGE |
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| Outline of Final Research Achievements |
To study atherosclerosis risk in diabetes, we investigated ATP-binding cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL) biogenesis in the liver and hepatocytes under hyperglycemic conditions.The following results were obtained . (1) The decrease of surface ABCA1 but increase of intracellular ABCA1 with high d-glucose in HepG2 cells. Clearance of ABCA1 was retarded both in primary hepatocytes and HepG2 cells exposed to high d-glucose. (2) AGE-albumin reduced ABCA1 in J774 and THP-1 macrophages (20-30%) aInd induced a higher ABCA1 ubiquitination and a faster protein decay rate that was dependent on the presence of AGE during the kinetics of measurement in the presence of cycloheximide. (3) Zn++ increased ABCA1 expression, not by increasing the mRNA but by attenuating its decay rate, more prominently in the presence of cAMP. . (4) Nobiletin promotes the transcription of ABCA1/ABCG1, leading to the promotion of HDL production.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、ABCA1蛋白質の分解と安定化の詳細な分子機構を研究し、世界のHDL研究拠点の一つとしての研究成果を挙げてきた。ABCA1/ABCG1の発現と活性調節はHDL代謝制御の鍵であり、糖尿病においても脂質代 謝異常の改善と動脈硬化進展予防治療の重要な標的である。これらの成果は、HDL代謝の栄養学的制御、とりわけ糖尿病におけるそれの分子機構の解明につながり、ABCA1分解を標的としたHDL代謝改善／糖尿病動脈硬化進展予防／治療に新たな道を開くことができる。
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