APJは,心筋縮における二重受容体として作用する
Maria Cecilia Scimia1, Cecilia Hurtado, Saugata Ray
1Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
Nature
|July 20, 2012
まとめ
APJ受容体の遺伝的喪失は,メカノセンサとして作用することで,心筋縮と心不全を予防します. APJは,機械的なストレッチとアペリンのシグナリングを結びつけ,心臓筋の成長を調節します.
科学分野:
- 心臓病学 心臓病学
- 分子生物学は分子生物学である.
- 生理学 生理学とは
背景:
- 心筋縮は,持続的な過負荷に対する適応反応ですが,その病理的進行は心不全につながる.
- APJ受容体とそのリガンドアペリンは,心血管の調節に関与しています.
研究 の 目的:
- APJ受容体の心筋縮および心不全における役割を調査する.
- APJが機械的刺激とペプチドリガンドに対する細胞反応を媒介するメカニズムを解明する.
主な方法:
- 遺伝的機能喪失モデル (APJ-nullマウス) とリガンド欠乏モデル (アペリン-nullマウス) を利用した.
- 機械的なストレッチとアペリン刺激に対する心筋細胞の反応を評価した.
- Gタンパク質とβ-アレスティンの関与を含む下流信号伝達経路の調査.
主要な成果:
- APJ-nullマウスは,慢性的な圧力過負荷誘発性心筋縮および心不全に対する有意な抵抗を示した.
- APJは,心筋細胞のメカノセンサとして機能し,ストレッチに対する反応として高縮を媒介する.
- ストレッチ誘発のAPJ活性化はGタンパク質独立であり,アペリン誘発の活性化はGαi依存である.
- β-アレスティンのノックダウンまたは薬理学的アペリン治療は,ストレッチ媒介性縮を阻害しました.
結論:
- APJは,機械的なストレッチとペプチドアペリンの両方を感知する二機能受容体です.
- APJは,機械的過負荷と心筋細胞高縮および心不全の進行を結びつける上で重要な役割を果たします.
- APJ経由でストレッチとアペリンによって活性化される明確なシグナル伝達経路は,心臓適応における複雑な規制メカニズムを強調しています.
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