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グルタミン合成酵素のグルタミン合成以外の血管新生における役割
Guy Eelen1,2,3, Charlotte Dubois4,5, Anna Rita Cantelmo4,5,6
1Center for Cancer Biology, University of Leuven, Leuven, Belgium. guy.eelen@kuleuven.vib.be.
Nature
|August 31, 2018
まとめ
グルタミン合成酵素 (GLUL) は,RHOJをパルミトイロ化することによって,内皮細胞の移動と病理的血管新生を調節する. 血管の芽生えを阻害し,健康な細胞に影響を及ぼさず,病気に関連した血管新生を阻害する.
科学分野:
- 分子生物学
- 細胞生物学
- 血管生物学
背景:
- グルタミン合成酵素 (GLUL) は,グルタミン酸とアンモニアをグルタミン酸に変換する酵素である.
- 内皮細胞はGLULを発現しますが,生理学的レベルではグルタミン合成活動は最小です.
- 内皮細胞におけるGLULの非正規的機能は,ほとんど未研究のままである.
研究 の 目的:
- 血管の発達と血管新生における内皮のGLULの役割を調査する.
- 内皮細胞移動におけるGLULの機能の基礎となる分子メカニズムを解明する.
- 病理的血管新生におけるGLUL阻害の治療的可能性を決定する.
主な方法:
- マウスモデルにおけるGlulの遺伝的消去
- グルタミン合成酵素の薬理学的抑制
- 人間の静脈内皮細胞 (HUVEC) を用いたインビトロ研究
- 内皮細胞の移動,増殖,RHOJの局所化,およびRhoキナーゼのシグナリングの分析.
主要な成果:
- 血管の芽生えを阻害する.
- GLUL抑制は,眼や炎症性疾患では血管新生を抑制しますが,健康な成人の血管系では抑制されません.
- RHOJ膜の局所化と活性化を減らし,内皮細胞の移動を阻害する.
- GLULはRHOJのパルミトイレーションと直接相互作用し,その活性化に不可欠です.
結論:
- グルタミン合成酵素は,内皮細胞の移動と病理的血管新生を調節する新しい非正規の役割を持っています.
- 血管新生におけるGLULの機能は,RHOJのパルミトイレーションと活性化によって媒介される.
- GLULをターゲットにすることで,血管新生に関連する疾患の治療戦略を提供することができます.
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