レッドワインに含まれるポリフェノル系フィトアレキシンであるレスベラトロールは,内皮の酸化窒素合成酵素の発現と活性を高めます
Thomas Wallerath1, Göran Deckert, Thomas Ternes
1Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
Circulation
|September 25, 2002
まとめ
ぶどうに含まれるレスベラトロールは,ヒト細胞の内皮酸化窒素合成酵素 (eNOS) 発現と酸化窒素 (NO) 産生を刺激する. この植物エストロゲンは,
科学分野:
- 心血管科学 心血管科学
- 分子生物学は分子生物学である.
- 薬理学 薬理学とは
背景:
- エストロゲンは,プロモーター活性とSp1転写因子結合を通じて,内皮酸化窒素合成酵素 (eNOS) を上調する.
- 葡萄のフィトアレキシンであるレスベラトロールは,エストロゲン受容体のアゴニストとして作用する.
- 本研究では,人間の内皮細胞におけるeNOS発現に対するレスベラトロールの影響を調査しています.
研究 の 目的:
- レスベラトロールが内皮の酸化窒素合成酵素 (eNOS) 発現に影響を与えるかどうかを判断する.
- レスベラトロールがeNOSに影響するメカニズムを探求する.
- 酸化窒素 (NO) 産生に対するレスベラトロールの短期的および長期的影響を評価する.
主な方法:
- ヒト静脈内皮細胞 (HUVEC) とEA.hy 926細胞をレスベラトロールでインキュベートした.
- eNOS mRNAおよびタンパク質発現,プロモーター活性,およびNO産生を測定した.
- 転写因子結合を評価するために,電泳性移動シフトアッセイ (EMSA) が使用されました.
- エストロゲン受容体の役割は,アンタゴニストを用いて調査されました.
主要な成果:
- レスベラトロールの投与量と時間によって上調されたeNOS mRNA (最大2.8倍) とタンパク質発現.
- eNOSプロモーターの活性が増加し,近辺263bpまで局所化されたことが観察されました.
- レスベラトロールは,エストロゲン受容体対抗性とは独立して,eNOS mRNAを安定させ,NOの産生を強化した.
- 短期インキュベーションにより,生物活性なNOの産生も増加した.
結論:
- レスベラトロールは,eNOSの発現と活動を刺激します.
- この刺激は,レスベラトロールの心臓血管保護効果に寄与する可能性があります.
- このメカニズムは,エストロゲン受容体を通してのみならず,eNOSに直接的な影響を及ぼします.
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