窒素酸化物による低酸素における細胞内酸素の再分配:HIF1alphaに及ぼす影響

Thilo Hagen¹, Cormac T Taylor, Francis Lam

¹Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.

Science (New York, N.Y.)

|December 13, 2003

まとめ

酸化窒素は,低酸素状態で低酸素誘導因子 (HIF) の安定化を防ぐ. これは,酸化窒素が酸素をプロリルヒドロキシラーゼに誘導し,HIFの分解を増加させ,低酸素に対する細胞の反応を変更するからです.

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.
生理学生理学とは

背景:

細胞は低酸素 (低酸素) に反応し,低酸素誘導因子 (HIF) 1alpha.
HIF-1αは,糖分解と血管新生に関与する遺伝子を調節する転写因子です.
酸化窒素とミトコンドリア呼吸阻害剤は,低酸素期におけるHIF-1αの安定化を阻害する.

研究の目的:

窒素酸化物が低酸素症におけるHIF-1α安定化を阻害するメカニズムを調査する.
この過程におけるプロリルヒドロキシラーゼ依存分解の役割を調査する.
ミトコンドリアの呼吸抑制が細胞内酸素配分とシグナル伝達にどのように影響するかを理解する.

主な方法:

研究は培養細胞を用いて行われました.
HIF-1alphaのプロリルヒドロキシラーゼに依存する分解を評価した.
レニラルシフェラーゼは,細胞内酸素濃度を測定するために使用されました.

主要な成果:

酸化窒素およびミトコンドリア呼吸阻害剤は,プロリルヒドロキシラーゼに依存したHIF-1alphaの分解を増加させます.
低酸素期間のミトコンドリア呼吸の抑制は,酸素の再分配につながります.
酸素は,プロリルヒドロキシラーゼのような非呼吸器の標的に誘導され,低酸素シグナリングを防ぐ.

結論:

酸化窒素は,低酸素による細胞信号伝達の影響を深刻に変化させます.
観察された効果は,HIF-1alpha.の強化された分解によって媒介されます.
細胞内酸素再分配は,低酸素反応の調節に重要な役割を果たします.

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