血清プロプロテインコンバーターゼサブチリシン/ケキシン9型と細胞表面低密度リポプロテイン受容体:相互調節の証拠
Hagai Tavori1, Daping Fan, John L Blakemore
1Vanderbilt University, Cardiovascular Medicine, Nashville, TN 37232-6300, USA.
Circulation
|May 22, 2013
まとめ
低密度脂質タンパク質 (LDL) 受容体 (LDLR) は,プロプロテインコンバーターゼサブチリシン/ケキシン9型 (PCSK9) をクリアする主要な経路である. このLDLRとPCSK9の相互調節により,コレステロールレベルが制御されます.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 心血管科学 心血管科学
背景:
- プロプロテイン変換酵素サブチリシン/ケキシンタイプ9 (PCSK9) は,低密度リポプロテイン受容体 (LDLR) の分解を調節し,血清コレステロールに影響を及ぼします.
- 欠陥LDLRは高コレステロール血症を引き起こすが,PCSK9クリアランスには影響しない.
研究 の 目的:
- PCSK9とLDLRの相互相互作用を調査する.
- 血清コレステロールレベルに対するそれらの組み合わせた効果を決定するために.
主な方法:
- 人間のPCSK9.9を発現するトランスジェニックマウスの生成.
- 様々な組織 (肝臓,腎臓,副腎) でのLDLR分解の分析.
- 血清PCSK9とコレステロールレベルを野生型,LDLR ((-/-)),LDLR ((+/-)) のマウスで測定した.
主要な成果:
- 人間のPCSK9は,腎臓発現にもかかわらず,主に肝臓におけるLDLRの分解を引き起こした.
- PCSK9は,LDLRとは無関係にリポタンパク質の肝臓分泌を増加させた.
- PCSK9発現は血清のPCSK9レベルを上昇させ,LDLR発現は減少させました.
- PCSK9のクリアランスは,機能的なLDLRの存在において,著しく速かった.
結論:
- LDLRはPCSK9の除去の主な経路である.
- LDLRとPCSK9.9の間には相互の規制関係が存在する.
- この相互作用は,血清のPCSK9,肝臓のLDLR発現,そして最終的には血清のLDLレベルを支配する.
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