Identification of regulation factor for oxysterol production in FBS and its nobel signal transduction
Project/Area Number |
15K08284
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General medical chemistry
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Research Institution | Dokkyo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
安戸 博美 獨協医科大学, 医学部, 助教 (10704885)
青山 智英子 獨協医科大学, 医学部, 助教 (90420778)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | オキシステロール / コレステロール25-ヒドロキシラーゼ / 25ーヒドロキシコレステロール / コレステロール25ヒドロキシラーぜ / HMG-CoAレダクターゼ / ET / 25-ヒドロキシコレステロール / シチジリルトランスフェラーゼ / コレステロール25-ヒドロキシラーゼ / Fetal bovine serum / 25-ヒドロキシコレステロール / コレステロール25ヒドロキシラーゼ / コレステロール / ホスホエタノールアミン / シチジルトランスフェラーゼ |
Outline of Final Research Achievements |
Oxysterols are hydrolyzed cholesterol and one of which such as 25-hydroxycholesterol suppressed transcription of rate limiting enzymes for cholesterol and phospholipid biosynthesis (phosphatidylethanolamine (PE)), HMG-CoA reductase and CTP:phosphoethanolamine citydylyltransferase, respectively. In this study, 25-hydroxycholesterol was found to suppress the interaction between NF-Y and p300 on their enzyme promoters and suppressed their transcription. Therefore, we were interested in the regulation of 25-hydroxycholesterol concentration in cells and regulation of transcription and enzyme activity of cholesterol 25-hydroxylase which catalyze cholesterol to 25-hydroxycholesterol in cells. We found that unknown factors in fetal bovine serum suppressed transcription and enzyme activity of cholesterol 25-hydroxylase, are now tring to purify the factor which may be a glycoprotein.
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Academic Significance and Societal Importance of the Research Achievements |
25-HCは細胞膜を構成するコレステロールやリン脂質合成酵素の転写を抑制し、細胞増殖に深く関与することが推定される。また、マクロファージがインターフェロンにより刺激を受けるとCH25Hの転写が促進し、25-HCが放出され、paracrine様に25-HCが抗ウイルス作用を示すことが報告された(Cell Immunity, 2017)。本研究で見出した、FBS中のCH25H転写抑制因子の同定と治療目的の除去や阻害剤の開発は、ウイルス疾患や細胞増殖の盛んながんの治療、およびオキシステロールが脂肪酸合成を調節することからメタボリック症候群などの脂質代謝異常症などの治療への応用も期待できる。
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Report
(5 results)
Research Products
(23 results)
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[Journal Article] Changes of plasmalogen phospholipid levels during differentiation of induced pluripotent stem cells 409B2 to endothelial phenotype cells2017
Author(s)
Yusuke Nakamura, Yasuo Shimizu, Yasuhiro Horibata, Rinna Tei, Ryosuke Koike1, Meitetsu Masawa, Taiji Watanabe, Taichi Shiobara, Ryo Arai, Kazuyuki Chibana, Akihiro Takemasa, Hiroyuki Sugimoto, Yoshiki Ishii
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Journal Title
Scientific Reports
Volume: 7
Pages: 1-9
DOI
Related Report
Peer Reviewed
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[Journal Article] Matrix-assisted laser desorption/ionization imaging mass spectrometry reveals changes of phospholipid distribution in induced pluripotent stem cell colony differentiation.2017
Author(s)
Shimizu Y, Satou M, Hayashi K, Nakamura Y, Fujimaki M, Horibata Y, Ando H, Watanabe T, Shiobara T, Chibana K, Takemasa A, Sugimoto H, Anzai N, Ishii Y.
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Journal Title
Anal Bioanal Chem.
Volume: 291
Pages: 1007-1016
DOI
Related Report
Peer Reviewed
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[Journal Article] Protein purification and cloning of diacylglycerol lipase from rat brain.2016
Author(s)
Aso C, Araki M, Ohshima N, Tatei K, Hirano T, Obinata H, Kishi M, Kishimoto K, Konishi A, Goto F, Sugimoto H, Izumi T.
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Journal Title
J Biochem.
Volume: 159
Pages: 585-597
DOI
Related Report
Peer Reviewed
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