ヘモグロビンαの内皮細胞発現は,酸化窒素のシグナル伝達を調節する

Adam C Straub¹, Alexander W Lohman, Marie Billaud

¹Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908, USA.

Nature

|November 6, 2012

まとめ

内皮のヘモグロビンアルファは,血管内の窒素酸化物 (NO) 信号伝達を調節する. その酸化状態はNOの生物利用性を制御し,血管の反応性と血流に影響を与えます.

科学分野:

心血管生物学心血管生物学
細胞生化学細胞生化学
分子生理学分子生理学

背景:

酸化窒素 (NO) 合成酵素 (NOS) のシグナル伝達は,血管機能に不可欠ですが,単純な拡散モデルは,その調節を不十分に説明します.
内皮のNOSは血圧と血流を調節しますが,正確なメカニズムは不明です.

研究の目的:

内皮細胞内のNOシグナル伝達調節のための新しいモデルを調査する.
NOの生物利用性と血管の反応性を調節するヘモグロビンα (Hbα) の役割を特定する.

主な方法:

人間とマウスの動脈内皮細胞におけるHb αの表現分析.
Hb αの遺伝的枯渇により,その機能的影響を評価する.
Hb α酸化状態の調節におけるサイトクロームb5還元酵素3 (CYB5R3) の役割を調査する.
NOのバイオアクティビティを測定するためにCYB5R3の薬理学的抑制.

主要な成果:

ヘモグロビンアルファ (Hb α) は動脈内皮細胞で発現し,筋内皮の交差点に局所されています.
内皮のHb αは血管の反応性を調節し,その遺伝的欠如は,この機能を無効にします.
Hb αのFe(3+) 状態はNOシグナル伝達を促進し,CYB5R3によるFe(2+) 状態への還元はそれを阻害する.
CYB5R3を抑制すると,小動脈におけるNOのバイオアクティビティが強化されます.

結論:

NOシグナル伝達調節のための新しいメカニズムには,内皮のHb α.の細胞内酸化状態が含まれています.
このHbα依存のNOS信号の調節は,血管機能にとって非常に重要です.
この発見は,様々な体細胞の他のヘムを含むグロービンにも適用される可能性がある.

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