| Project/Area Number |
24590358
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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 |
General medical chemistry
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Chieko 獨協医科大学, 医学部, 助教 (90420778)
SATOU Motoyasu 獨協医科大学, 医学部, 助教 (20418891)
HORIBATA Yasuhiro 獨協医科大学, 医学部, 助教 (80392116)
ANDO Hiromi 獨協医科大学, 医学部, 助教 (10704885)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | オキシステロール / ホスホエタノールアミン / シチジリルトランスフェラーゼ / HMG-CoAレダクターゼ / NF-Y / 25-ヒドロキシコレステロール / ホスファチジルエタノールアミン / コレステロール / Yin Yang1 / Phosphatidylethanolamine / CTP:phosphoethanolamine / Cytidylyltransferase / 25-hydroxycholesterol / HMG-CoA reductase / YY1 |
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| Outline of Final Research Achievements |
ET (CTP:phosphoethanolamine cytidylyltransferase) is the rate-limiting enzyme in mammalian PE (phosphatidylethanolamine) synthesis. We found that ET mRNAlevels increased in cells after serum starvation, an effect that could be suppressed by low-density lipoprotein or 25-HC (25-hydroxycholesterol). Transcription of Hmgcr, which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, is also suppressed by 25-HC. Nevertheless, a sterol-regulatory element was not detected in the Pcyt2 promoter region. The important element for transcriptional control of ET by 25-HC (1.25 μM) was determined to reside between －56 and －36 and NF-Y (nuclear factor-Y) binds the site. Moreover, NF-Y binds to the Hmgcr promoter in gel-shift analysis. ChIP analysis revealed that 25-HC inhibited the interaction between NF-Y and RNA polymerase II on the Pcyt2 and Hmgcr promoters. We conclude that NF-Y is important for the basal transcription of Pcyt2 and is involved in the inhibitory effects of 25-HC.
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