前期使用AICAR治疗导致C2C12细胞中mTOR基质的选择性酸化
Cass J Dedert1, Kazimir R Bagdady1, Jonathan S Fisher1
1Department of Biology, Saint Louis University, St. Louis, MO 63103, USA.
Current issues in molecular biology
|October 27, 2023
概括
骨肌细胞中的代谢压力可以长期改变细胞通路. 之前接触AICAR会选择性地影响mTOR基质,即使在恢复后,这表明对细胞代谢的持续影响.
科学领域:
- 细胞生物学 细胞生物学
- 代谢信号传递 代谢信号传递
- 骨肌肉生理学 骨肌肉生理学
背景情况:
- 骨肌肉的代谢压力会引起持久的变化,但潜在的机制仍然不清楚.
- AMP激活蛋白激酶 (AMPK) 在细胞能量恒温中起着至关重要的作用.
- 拉巴胺素 (mTOR) 途径的机械性标是细胞生长和新陈代谢的核心.
研究的目的:
- 研究AMPK激活对C2C12骨肌细胞代谢途径和信号激酶的长时间影响.
- 阐明AICAR暴露影响mTOR信号和基质酸化的特定机制.
- 检查不同恢复介质对AICAR治疗后代谢反应的影响.
主要方法:
- 用AICAR治疗C2C12神经细胞,这是AMPK激活剂.
- 对包括ULK1,S6K和Akt在内的关键标蛋白质酸化的分析.
- 评估葡萄糖-6酸盐脱酶活性.
- 在不同的恢复介质 (DMEM与KHB缓冲区) 中评估细胞反应.
- 使用拉巴胺素和PP242.的mTOR复合物的药理抑制.
主要成果:
- 艾卡尔急剧增加了AMPK,mTORC1和mTORC2位的酸化.
- 对葡萄糖-6酸盐脱酶活性的长期影响取决于恢复条件.
- 根据回收介质观察到mTORC1和mTORC2基质 (S6K,ULK1,Akt) 的化差异.
- 抑制剂研究揭示了mTORC1和mTORC2在调解这些酸化事件中的不同作用.
结论:
- 之前的AICAR暴露会诱导骨肌细胞中mTOR基质的选择性和持续酸化.
- 恢复条件显著影响长期的代谢和信号适应.
- 这些发现突出了AMPK,mTOR信号传递和应对压力的代谢调节之间的复杂相互作用.
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