ヒストンデアセチラーゼ4のO-GlcNAcylationは,糖尿病患者の心臓を障害から保護する
Mariya Kronlage1,2,3, Matthias Dewenter1,3, Johannes Grosso1,3
1Institute of Experimental Cardiology (M.K., M.D., J.G., U.O., L.H.L., J.B.), Heidelberg University, Germany.
Circulation
|June 15, 2019
まとめ
ヒストン脱酸化素4 (HDAC4) は糖尿病患者の心臓を保護する. Ser-642でのHDAC4のO-GlcNAcylationは,有害なシグナル伝達と糖尿病性心筋病の予防に作用する.
科学分野:
- 心血管生物学
- 代謝障害
- 分子心臓科
背景:
- 糖尿病と心不全はしばしば共存し,公衆衛生に影響を及ぼします.
- 糖尿病の代謝が心臓の機能に どう影響するかを理解することが重要です
- 逆説的に 血糖値を下げる薬は 心不全を悪化させ 複雑な血糖信号を強調します
研究 の 目的:
- 糖尿病性心臓病におけるヒストン脱酸化酵素4 (HDAC4) の役割を調査する.
- 血糖代謝が心臓の信号伝達に影響を与える分子機構を解明する.
- 糖尿病性心筋病の潜在的治療標的を特定する
主な方法:
- 心筋細胞特異的なHDAC4ノックアウトマウスを生成した.
- 1型 (ストレプトゾトシン) と2型 (dB/dB) の糖尿病モデルを使用した.
- 心臓機能の評価と再構築
- グルコースとO-GlcNAcylationがHDAC4に与える影響を in vitroとin vivoで研究した.
主要な成果:
- HDAC4欠乏症は糖尿病のマウスの心不全を悪化させる.
- 高血糖/高O-GlcNAc条件下では,HDAC4の心臓を保護するN端の断片が強化される.
- HDAC4のO-GlcNAcylationは,セル-642での保護断片の生成に不可欠であり,セル-632での有害なリン酸化に対抗する.
結論:
- HDAC4は,糖尿病において重要な心臓保護的役割を果たします.
- HDAC4のO- GlcNAcylationは,糖尿病性心筋病に対する重要な防御メカニズムである.
- この翻訳後の改変の理解は 糖尿病患者の心不全の治療の可能性を 提供します
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