Identification of a novel regulatory mechanism for phospholipid and cholesterol biosynthesis by cholesterol derivatives.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Ando Hiromi 獨協医科大学, 医学部, 助教 (10704885)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: リン脂質 / コレステロール / 細胞膜 / ヒストンアセチル化 / p300

Outline of Final Research Achievements

Phosphatidylethanolamine (PE) is a major phospholipid component of mammalian cell membranes. CTP:phosphoethanolamine cytidylyltransferase (ET) is a rate-limiting enzyme of PE biosynthesis. Previously, I reported that oxysterols such as 25-hydroxycholesterol (25-HC) suppress ET transcription. The transcription of ET is decreased by 25-HC via the inhibition of p300 recruitment to the ET promoter by NF-Y and suppression of histone acetylation. In this study, direct binding of p300 and NF-YB was not observed. Therefore, I performed DNA pulldown assay and showed that p300 and NF-YB bound to the ET promoter, and 25-HC suppressed p300 binding to the ET promoter, but not NF-YB.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

哺乳動物の細胞膜は主にホスファチジルコリン (PC) やホスファチジルエタノールアミン (PE) などのリン脂質で構成される。これら脂質の組成比が一定である事は細胞膜の安定性に大きく関与し、「PC/PE比の異常」は強く疾患と関係する。肝臓の場合、脂肪肝や肝不全となる。そのため、PC, PEの合成制御機構の解明は上記の疾患の理解に繋がると考えられるが、PC合成の律速酵素CTαに比べ、PE合成の律速酵素ETの転写制御機構は未だ不明な点が多く残っている。したがって、PE合成制御機構の解明により上述の疾患の発生機構の理解や治療応用への基礎的な知見を得ることができる。