昼夜时钟系统在线粒体转硫路径和组织重塑中的作用
Suresh C Tyagi1, Sathnur Pushpakumar1, Utpal Sen1
1Department of Physiology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Canadian journal of physiology and pharmacology
|November 18, 2023
概括
硫化 (H2S) 通过影响转硫路径和昼夜时钟,影响骨肌肉. 在小鼠中,H2S治疗改善了途径受损的肌肉健康.
科学领域:
- 生物化学 生物化学
- 时间生物学 时间生物学
- 骨肌肉生理学 骨肌肉生理学
背景情况:
- 硫化 (H2S) 是一种参与转硫化途径的代谢气体,对同类 (Hcy) 代谢和减轻骨肌肉重塑至关重要.
- 由BMAL 1调节的昼夜时钟影响Hcy代谢,但其对骨肌肉中转硫化途径的影响尚不清楚.
研究的目的:
- 为了研究昼夜时钟对骨肌肉中转硫化途径的影响.
- 为了确定H2S是否可以改善与昼夜时钟相关的骨肌肉代谢和再生中的干扰.
主要方法:
- 在睡眠和清醒周期期间评估血清矩阵金属蛋白酶 (MMP) 活动 (MMP-2,MMP-9,MMP-13) 在野生类型和囊氨酸β合成酶缺乏 (CBS-/+) 的小鼠中.
- 在骨肌组织中测量过硫化因子 (CBS,CSE,MTHFR,PEMT,PON1) 和线粒体蛋白质 (PGC-1α,MFN-2).
- 对小鼠进行H2S治疗,以评估其治疗效果.
主要成果:
- 与睡眠相比,小鼠在清醒期间表现出强大的MMP激活,这表明在肌肉衰竭中观察到的"1-碳代谢失调"的联系.
- 在CBS-/+小鼠中,转硫因子减弱,但H2S治疗恢复了这些水平.
- H2S干预显著改善了线粒体再生标志物 (PGC-1α,MFN-2).
结论:
- 昼夜时钟在调节转硫路径方面发挥作用,影响骨肌肉重塑.
- H2S在减轻与昼夜节律障碍和代谢失衡相关的骨肌功能障碍方面显示出治疗潜力.
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