Endogenous choline production through phospholipid catabolism
Project/Area Number |
18K06978
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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 |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
HIRABAYASHI Tetsuya 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主席研究員 (90345025)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | コリン / グリセロホスホコリン / リゾホスホリパーゼ / メチル基 / 肝臓 / 神経変性 / ホスホリパーゼA2 / リン脂質 / 筋萎縮 / ホスファチジルコリン / リン脂質分解 / メタボロミクス |
Outline of Final Research Achievements |
We have shown that the iPLA2gamma/iPLA2theta/glycerophosphoesterase axis functions as an intrinsic choline production pathway that mobilizes free choline from the membrane phospholipids to supply methyl groups in the liver. This pathway is necessary for the methionine regeneration and normal liver function. Moreover, CNS-specific iPLA2delta and iPLA2theta deficiency causes profound neuronal degeneration and muscle atrophy, indicating that these lysohpspholipases have crucial roles in the survival of neurons including motor neurons.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で明らかとした肝臓と神経系における内因性コリン産生系の役割は、脂肪肝、神経変性、筋萎縮などの疾患群とリン脂質代謝経路の関連性を示唆し、従来想定されていたリゾホスホリパーゼの概念を大きく転換するものである。将来的にリン脂質分解酵素の機能介入を通じて肝機能、神経機能、骨格筋機能を人為的に調節できるようになれば、新しい分子機序に基づく健康食品・医薬品の開発に結びつくことが期待される。
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation2020
Author(s)
Takeichi T, Hirabayashi T, Miyasaka Y, Kawamoto A, Okuno Y, Taguchi S, Tanahashi K, Murase C, Takama H, Tanaka K, Boeglin WE, Calcutt MW, Watanabe D, Kono M, Muro Y, Ishikawa J, Ohno T, Brash AR, Akiyama M
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Journal Title
J Clin Invest
Volume: 130
Issue: 2
Pages: 890-903
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling.2019
Author(s)
Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 116(41)
Issue: 41
Pages: 20689-20699
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] SDR9C7 catalyzes the critical dehydrogenation of acylceramides for skin barrier formation2021
Author(s)
T Takeichi, T Hirabayashi, Y Miyasaka, A Kawamoto, Y Okuno, S Taguchi, K Tanahashi, C Murase, H Takama, K Tanaka, W Boeglin, M Calcutt, D Watanabe, M Kono, Y Muro, J Ishikawa, T Ohno, AR Brash and M Akiyama
Organizer
Society for Investigative Dermatology 2021
Related Report
Int'l Joint Research
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