足以进行远程缺血性保护的EGLN1抑制和转向
Benjamin A Olenchock1, Javid Moslehi2, Alan H Baik3
1Division of Cardiovascular Medicine, Department of Medicine, The Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|February 27, 2016
概括
抑制Egln1可以保护器官免受缺血损伤. 这种保护涉及α-甲酸 (αKG) 和氨酸 (KYNA),作为远程缺血预调的信号分子.
科学领域:
- 生物医学
- 生理学
- 分子生物学
背景情况:
- 缺血预调可以保护器官免受长期缺血的影响.
- 远程缺血预制 (RIPC) 需要远程保护.
- 艾格林在调解预先条件的作用尚未完全被理解.
研究的目的:
- 调查抑制αKG依赖的二氧化酶Egln1是否可以调解局部和远程缺血预调.
- 确定Egln1介导的对心肌缺血再输血 (I/ R) 损伤的分子机制.
主要方法:
- 有体基因缺失和EGLN1的药理抑制的小鼠模型.
- 对 Egln1 的全身和骨肌的特定抑制.
- 在RIPC中研究系统因素的准生物体实验.
- 测量循环中的αKG和肝酸 (KYNA) 水平.
主要成果:
- 针对心肌I/ R损伤的EGln1受保护小鼠的系统或骨肌肉抑制.
- RIPC是由一个分泌的因子介导的,并通过对生物体的实验得到证实.
- 抑制EGLN1导致血液中的αKG增加,导致肝脏KYNA的产生.
- KYNA被认为是必要且足够的心脏保护媒介.
结论:
- 抑制Egln1足以调解局部和远程缺血预调.
- 循环中的αKG积累和随后的肝脏KYNA产生是关键机制.
- 在该模型中,氨酸 (KYNA) 作为缺血性保护的关键信号分子.
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