酸化された低密度リポプロテインは, pertussis toxin-sensitive G-protein経路を通じて,内皮の基礎線維芽細胞成長因子を低調化する:血小板活性化因子のようなフォスホリピドの媒介者の役割
1Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Circulation
|August 2, 2001
まとめ
酸化LDL (oxLDL) は,基礎線維芽細胞成長因子 (bFGF) のダウンレギュレーションにより,内皮細胞の成長を抑制する. これは,特定のフォスフォリピドを含む, pertussis toxin-sensitive G-protein経路を通じて発生する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 酸化LDL (oxLDL) は血管新生を阻害することが知られている.
- この阻害は,部分的に,内皮の基礎線維芽細胞成長因子 (bFGF) のダウンレギュレーションによって媒介されます.
- 信号伝達経路の正確な経路は,まだ解明されていない.
研究 の 目的:
- oxLDLが内皮のbFGFをダウンレギュレーションするメカニズムを調査する.
- 特定の信号伝達経路と関連する潜在的なフォスフォリピド媒介体を特定するために.
主な方法:
- 牛の大動脈内皮細胞は,PBS,LDL,またはoxLDLで治療されました.
- 細胞は pertussis toxin (PTX) または特定の経路阻害剤で前処理された.
- bFGFのmRNA,タンパク質,DNA合成に対する効果を評価した.
- 血小板活性化因子 (PAF) 受容体アンタゴニスト (WEB 2086) とPAFアセチルヒドロラーゼが使用されました.
主要な成果:
- OxLDLは,bFGFのmRNA,タンパク質,DNA合成を著しく低下させた.
- 百日咳毒素 (PTX) の前治療は,oxLDLの抑制効果を阻害しました.
- MAPK,タンパク質キナーゼ,および細胞内Ca2+の阻害剤は,oxLDLの効果を弱めなかった.
- PAF受容体アンタゴニストはoxLDLの作用を阻害し,PAFの分解はoxLDLの効果を排除した.
結論:
- 酸化されたLDLは,内皮のbFGF発現とDNA合成を抑制する.
- このメカニズムは,PTX 感受性ヘトロトリメリック G タンパク質経路を含む.
- PAFに似ているが同一ではない媒介性リンパ脂が関与している.
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