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エストラディオール媒介の内皮酸化窒素合成酵素と熱ショックタンパク質90との結合は,アデノシンモノホスファート依存タンパク質キナーゼを必要とします
Eberhard Schulz1, Elad Anter, Ming-Hui Zou
1Evans Memorial Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass 02118, USA.
Circulation
|June 22, 2005
まとめ
エストラディオールは,内皮細胞におけるAMP活性化タンパク質キナーゼ (AMPK) を活性化させ,これは酸化窒素合成酵素 (eNOS) の活性化に不可欠である. この経路は熱ショックタンパク質90 (HSP90) を含み,NOの生物活性に影響を及ぼします.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
- 心血管研究 循環器科の研究
背景:
- エストラディオールは,様々なシグナル伝達経路を通じて,内皮酸化窒素合成酵素 (eNOS) を活性化します.
- AMP活性化タンパク質キナーゼ (AMPK) は細胞の適応に不可欠であり,他のホルモンによるeNOS活性化に関連している.
研究 の 目的:
- エストラディオールが内皮細胞におけるAMPKを活性化するかどうかを調査する.
- エストラディオール誘発のeNOS活性化におけるAMPKの役割を決定する.
主な方法:
- 豚の大動脈内皮細胞はエストラジオールで治療された.
- AMPKの活性化は,AMPKとアセチル-CoAカルボキシラーゼのリン酸化によって評価されました.
- 支配的陰性AMPKのアデノウイルス媒介発現とα1-AMPK-nullマウスでの研究が採用されました.
主要な成果:
- エストラジオルの時間および濃度に依存したAMPKが活性化され,AMPレベルとERalphaとは独立しているが,エストラジオルの代謝産物を必要とする.
- エストラディオールは,ENOSの触媒活性を増大させ,この効果は,支配的陰性AMPKによって逆転した.
- AMPKの阻害は,HSP90とのeNOSの相互作用を低下させ,マウスの血管におけるエストラディオール誘発のNO産生を低下させた.
結論:
- エストラディオール誘発のeNOS活性化には,AMPK活性化が不可欠である.
- AMPKは,HSP90とのeNOS相互作用を促進し,内皮細胞のNO生物活性を調節する.
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