饥饿通过矛盾的mTORC1信号保护肝细胞免受炎症损伤
Iqra Hussain1, Harini K Sureshkumar1, Michael Bauer1,2
1Department for Anesthesiology & Intensive Care Medicine, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), 07747 Jena, Germany.
Cells
|June 28, 2023
概括
卡路里限制通过激活AMPK和矛盾地激活mTORC1信号,保护肝细胞免受败血症引起的损伤. 这一途径增强了对炎症性压力的抵抗力,并维持了饥饿肝细胞中的蛋白质合成.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 与败血症相关的肝衰竭呈现出不良的预后.
- 在临床前的败血症模型中,卡路里限制增强了组织的弹性,并防止肝功能衰竭.
- 在肝衰竭中,卡路里限制的保护作用背后的分子机制在很大程度上是未知的.
研究的目的:
- 为了研究卡路里限制在肝细胞抵抗炎症损伤中的作用,使用永生肝细胞模型.
- 阐明关键营养/能量传感器系统 (AMPK,mTORC1,mTORC2) 对这种保护作用的贡献.
主要方法:
- 利用一个不朽的肝细胞细胞系来建模肝脏辅酶体.
- 应用遗传学和药理学方法来研究AMPK,mTORC1和mTORC2信号通路.
- 研究了抑制mTORC1 (使用药理剂或Raptor沉默) 对炎症应激下肝细胞存活率的影响.
主要成果:
- 饥饿 (卡路里限制) 保护肝细胞免受促炎性细胞因子诱导的损伤.
- 虽然AMPK和mTORC2对热量限制做出了预期的反应,但矛盾的是,mTORC1被饥饿细胞的炎症压力激活.
- 抑制mTORC1取消了饥饿和恶化的细胞死亡的保护作用,而mTORC1激活与自分离,但对蛋白质合成至关重要.
结论:
- 激活AMP激活蛋白激酶 (AMPK) 的参与和拉巴胺素复合物1 (mTORC1) 激活的悖论性机理性标介于在热量限制期间保护肝细胞免受益炎性压力.
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