通过S-nitroso-CoA减少酶系统进行代谢重编程,防止损伤
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
概括
通过调节新陈代谢,S-nitroso-CoA-SCoR系统保护脏免受损伤. 这涉及酸激酶M2 (PKM2) 的S- 化,平衡能量生产和细胞保护.
科学领域:
- 生物化学
- 分子生物学
- 脏生理学
背景情况:
- 内皮氧化合成酶 (eNOS) 提供脏保护,但机制尚不清楚.
- 通过S- 酸酶和酸酶调节的蛋白质S- 酸酶,调节细胞功能.
- 酵母中的S-nitroso-CoA (SNO-CoA) 和SNO-CoA减少酶 (SCoR) 系统具有一个未知作用的哺乳动物同类体AKR1A1.
研究的目的:
- 在哺乳动物中研究SNO-CoA-AKR1A1系统的生理作用.
- 阐明eNOS保护损伤的分子机制.
- 确定代谢和损伤的新调节剂.
主要方法:
- 使用了Akr1a1淘汰老鼠和Enos淘汰老鼠.
- 进行SNO蛋白鉴定的代谢分析和质谱.
- 在小鼠的近端管中进行向除酸酶M2 (PKM2).
主要成果:
- 删除Akr1a1增加了蛋白质S- 化,并防止了急性损伤.
- 当Enos也被删除时,保护就失去了,这表明对eNOS的依赖.
- 确定了PKM2的抑制性S-化作为一个关键机制,平衡糖解和酸突变.
结论:
- 在哺乳动物中,SNO-CoA-SCoR系统具有生理功能,调节代谢.
- 这种系统通过PKM2 S- 化提供了对急性损伤的保护.
- 这些发现为损伤和潜在的治疗目标提供了新的见解.
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