SRC-2コアクティベーターの欠如は,フォン・ジャーケ病に似たグリコゲノパシーを引き起こす
Atul R Chopra1, Jean-Francois Louet, Pradip Saha
1Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
まとめ
転写共活性化剤SRC-2は,G6Pase酵素を調節することによって,肝臓のグルコース生成を制御する. マウスのSRC-2欠乏症はフォン・ジャーケを模倣している.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 肝臓のグルコース生成は,脳の機能と生存に不可欠です.
- グルコース-6-ホスファタゼ (G6Pase) は,血にグルコースを放出する重要な酵素です.
- G6Paseの変異により,フォン・ジャーケ病 (グリコゲン貯蔵疾患-1a) が発症する.
研究 の 目的:
- 断食時の肝臓のグルコースの放出のレギュレータを特定するために.
- グルコース代謝における転写共同活性化剤SRC-2の役割を調査する.
- SRC-2がG6Pase発現を制御するメカニズムを解明する.
主な方法:
- 断食肝臓のグルコースの放出を調節するSRC-2の役割を調査した.
- 孤児核受容体RORalpha.とSRC-2の直接相互作用を分析した.
- マウスモデルにおけるSRC-2アブレーション (全身および肝臓特異的) の効果を調べた.
主要な成果:
- SRC-2は,断食肝臓のグルコース放出の調節剤として特定されました.
- SRC-2は,RORalpha.とコアクティベーターとしてG6Pase発現を直接調節する.
- ネズミのSRC-2除去により,フォン・ジャーケ病の現象型が生じた.
結論:
- SRC-2は肝臓のG6Pase発現の重要なレギュラーである.
- SRC-2は,哺乳類のグルコース産生を制御する上で重要な役割を果たします.
- SRC-2は,フォン・ジャーケ病の現象型を予防するために不可欠です.
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