Molecular mechanism of HDL reduction in diabetic malnutrition

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K00892
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Chubu University
• Principal Investigator: LU Rui 中部大学, 応用生物学部, 講師 (80381862)
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HDL / ABCA1

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.

Free Research Field

生化学、分子生物学、

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。