S- ニトロゾ- コア・リドゥクタゼ系による代謝再プログラムが腎臓損傷から保護する
Hua-Lin Zhou1, Rongli Zhang1, Puneet Anand1
1Institute for Transformative Molecular Medicine, Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Nature
|November 30, 2018
まとめ
S- ニトロゾ- CoA- SCoRシステムは,代謝を調節することにより,腎臓を損傷から保護します. これは,エネルギー生産と細胞保護のバランスをとる,ピルバートキナーゼM2 (PKM2) のS- ニトロシル化を含みます.
科学分野:
- 生物化学
- 分子生物学
- 腎臓生理学
背景:
- 腎臓に保護を与えるが,そのメカニズムは不明である.
- S- ニトロシラーゼとデニトロシラーゼによって媒介されるタンパク質S- ニトロシラーゼは,細胞機能を調節する.
- イーストのS-nitroso-CoA (SNO-CoA) とSNO-CoA還元酵素 (SCoR) システムには,未知の役割を持つ哺乳類の同類体AKR1A1があります.
研究 の 目的:
- 哺乳類におけるSNO-CoA-AKR1A1システムの生理学的役割を調査する.
- eNOSが腎臓損傷から保護する分子メカニズムを解明する.
- 腎臓の代謝と腎臓損傷の新たな調節物質を特定する.
主な方法:
- Akr1a1 ノックアウトマウスと Enos ノックアウトマウスを使った.
- SNOタンパク質の識別のための代謝プロファイリングと質量スペクトロメトリーが行われました.
- ネズミの近親腎管でピルバートキナーゼM2 (PKM2) の標的切除を行った.
主要な成果:
- Akr1a1の削除により,タンパク質S- ニトロシル化が増加し,急性腎臓損傷から保護された.
- 保護はEnosも削除され,eNOSへの依存を示しました.
- 重要なメカニズムとしてPKM2の抑制性S- 窒素化が特定され,糖分解とペントースリン酸シャントをバランスさせる.
結論:
- SNO-CoA-SCoRシステムは,腎臓の代謝を調節する哺乳類の生理学的機能を持っています.
- このシステムは,PKM2 S- ニトロシル化による急性腎損傷から保護します.
- 腎臓の損傷と 治療の標的について 新たな洞察を 提供しています
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