Rev-erbalphaは,代謝と昼間の経路を調整するヘムセンサーです
Lei Yin1, Nan Wu, Joshua C Curtin
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|November 17, 2007
まとめ
代謝に不可欠な分子であるヘムは,体内時計の重要な部分であるRev-erbalphaタンパク質と結合します. この相互作用は,日中時計,グルコースレベル,エネルギーバランスを制御するのに役立ちます.
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.
- クロノバイオロジーはクロノバイオロジーを用います.
背景:
- 昼間の時計は,哺乳類の代謝的ホメオスタシスを調節する.
- ヘムは酸化代謝と昼夜リズムに不可欠です.
- ヘムと昼夜調節の間の分子関連性は未知であった.
研究 の 目的:
- ヘムの二重機能を統合する昼夜系因子を特定する.
- ヘムが昼間のリズムと代謝に影響を与えるメカニズムを解明する.
主な方法:
- ヘムと孤児核受容体Rev-erbalpha.の相互作用を調査しました.
- コアプレッサー複合体とのRev-erbalphaの相互作用に対するヘムの効果を分析した.
- 肝臓のグルコーネオゲン遺伝子発現とグルコース出力に対するヘムの影響を評価した.
主要な成果:
- ヘムは,日中時計のコア成分であるRev-erbalphaに逆転的に結合する.
- ヘム結合は,核受容体コアプレッサー複合体とのRev-erbalphaの相互作用を調節する.
- ヘムは,肝臓のグルコネオゲン遺伝子発現と,Rev-erbalpha経由でグルコースの産生を抑制する.
結論:
- Rev-erbalphaはヘムセンサーとして機能します.
- このヘム感知メカニズムは,細胞の時計,グルコースホメオスタシス,エネルギー代謝を調整する.
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