ER压力被激活并参与了不使用诱导的肌肉缩
Lu Wang1,2, Xiangsheng Pang1,2, Shiming Li2
1State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 100094 Beijing, China.
Frontiers in bioscience (Landmark edition)
|August 1, 2023
概括
细胞内膜网膜 (ER) 压力是肌肉缩的关键驱动因素,由不使用引起. 用TUDCA抑制ER压力有效地防止了小鼠和非人类灵长类动物的肌肉损失和相关的分子变化.
科学领域:
- 分子生物学分子生物学
- 生理学 生理学 生理学
- 生物医学研究生物医学研究
背景情况:
- 消耗肌肉缩是一个重要的健康问题,降低生活质量和增加死亡率.
- 由蛋白质错误折叠引起的内质网膜 (ER) 压力会破坏细胞平衡,并与肌肉重塑有关.
- 在此之前,ER应激在不使用引起的肌肉缩中的作用尚不清楚.
研究的目的:
- 调查ER应激对不使用诱导的肌肉缩的影响.
- 为了确定是否抑制ER压力可以防止肌肉缩.
主要方法:
- 在小鼠中通过后肢卸载 (HU) 诱导肌肉缩,在 rhesus 中通过向下倾斜的卧床休息 (HDBR).
- 在HU期间给小鼠服用Tauroursodeoxycholic acid (TUDCA),一种ER压力抑制剂.
- 使用定量PCR,西式涂抹和免疫组织化学来分析分子和结构变化.
主要成果:
- 在HU期间,ER压力标志物和与缩相关的基因 (Atrogin-1,MuRF1,MUSA1) 同时上调.
- 通过AKT/FOXO3a通路,TUDCA治疗减轻了HU诱导的肌肉缩和无素合酶上调.
- 此外,TUDCA还抑制了HU诱导的氧化-至-糖解性肌纤维类型转换.
- 在HDBR诱导的 rhesus macaque soleus 肌肉缩中证实了 ER 应激激活.
结论:
- 在不同物种中,ER应激活与不使用引起的肌肉缩密切相关,并参与其中.
- 抑制ER压力是一种潜在的治疗策略,可以在不使用期间预防肌肉缩.
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