ERのストレス反応は,ヘプシディニンの誘導によって鉄代謝を制御する
Chiara Vecchi1, Giuliana Montosi, Kezhong Zhang
1Center for Hemochromatosis, Department of Internal Medicine, University Hospital Policlinico di Modena, Modena, Italy.
Science (New York, N.Y.)
|August 15, 2009
まとめ
炎症と同様に,エンドプラズマ網膜のストレスがヘプシジン産生を誘発し,鉄のレベルに影響を及ぼします. 転写因子CREBHは,このERストレス誘発のヘプシジンの発現を媒介し,タンパク質の品質管理と鉄の恒常性を結びつける.
科学分野:
- 分子生物学は分子生物学である.
- 生理学 生理学とは
- エンドクリノロジー エンドクリノロジー
背景:
- ヘプシジンは,肝臓で産生される鉄の恒常性の重要な調節剤です.
- ヘプシジンの調節不良は,炎症の貧血と血色腫症に関連しています.
- ヘプシジンの発現の既知の刺激には,炎症と鉄のレベルが含まれています.
研究 の 目的:
- ヘプシジンの発現を調節するエンドプラズマ網膜 (ER) ストレスの役割を調査する.
- ERストレスとヘプシジン産生を結びつける分子メカニズムを特定する.
主な方法:
- 毒素とタンパク質蓄積モデルを使用してマウスにおけるERストレス誘導.
- ヘプシジンの発現レベルと鉄分配分の分析 (ヒポフェレミア,の鉄分収縮).
- CREBHノックアウトマウスとプロモーターアッセイを用いた転写因子CREBHの役割の調査.
主要な成果:
- ERのストレスがヘプシジンの発現を誘発し,マウスでは低フェレミアと臓の鉄封じ込めにつながることが判明しました.
- 転写因子CREBHはヘプシジンのプロモーターと結合し,活性化させます.
- ERストレスによるヘプシディン誘導は,CREBHのノックアウトマウスで低下した.
結論:
- ERストレスは,ヘプシジンの発現のための新しい細胞外刺激である.
- CREBHは,ERストレスによるヘプシディン調節の重要な媒介である.
- この発見は,細胞タンパク質の品質管理機構を先天的免疫と全身的な鉄代謝と関連付けています.
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