心不全の進行中のタンパク質ファスファタゼ1相互作用体の再配置
David Y Chiang1,2,3, Katherina M Alsina2,4, Eleonora Corradini3,5
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.Y.C.).
Circulation
|April 20, 2018
まとめ
心不全 (HF) でのタンパク質ファスファタゼ1 (PP1) 相互作用の変化 Ppp1r7を含む主要な相互作用因子は,HFの進行と関連しており,この複雑な心臓病に対する新しい治療目標を提供することができる.
科学分野:
- 心血管生物学
- 分子心臓科
- プロテオミクス
背景:
- 治療の進歩にもかかわらず,心不全 (HF) の罹患率は増加しています.
- HFの病原性におけるタンパク質フォスファタゼ1 (PP1) の役割は不明である.
- 以前の研究では,PP1触媒サブユニット (PP1c) に焦点を当て,そのインタラクタを無視した.
研究 の 目的:
- 心臓のPP1インタラクトームを定義する.
- HFの進行中にPP1インタラクトームが再編成されるかどうかをテストする.
- HFに関連した特定のPP1cインタラクタを特定する.
主な方法:
- 横動脈収縮によるHF誘導
- PP1cの親和性浄化と,相互作用者を特定するための質量スペクトロメトリー.
- PP1 調節サブユニット7 (Ppp1r7) のノックダウンとカルシウムイメージング
主要な成果:
- 71の心臓および98のHeLa PP1cインタラクタが特定され,最大のPP1インタラクトームデータセットを形成した.
- Ppp1r7を含む9つのPP1cインタラクターは,HFの進行に関連した変化した結合を示した.
- 心臓Ppp1r7のノックダウンにより 心臓機能障害とカルシウム放出が妨げられました.
結論:
- PP1インタラクトームは,HFの進行中に重要な再配置を受けます.
- HFの進行に関連した9つの主要なPP1インタラクタは,潜在的な治療標的である.
- Ppp1r7は,HFにおけるPP1インタラクトームを調節する分子スポンジとして作用する.
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