内质网应激通过AKT-TSC-mTOR信号通路调控自噬
发布时间：2018-10-05 09:44
【摘要】： 内质网是真核细胞一种重要的细胞器,是细胞内蛋白质合成,修饰,折叠的场所。由于各种原因引起的内质网平衡的紊乱,称为内质网应激。内质网应激会引起从内质网到细胞质和细胞核的信号传导,最终帮助细胞恢复稳态并得以存活。然而,严重的内质网应激可导致细胞发生自噬和凋亡。对于调控这一过程的精确机制目前知之甚少。本研究表明,内质网应激通过抑制mTOR通路引起细胞自噬,进而诱导细胞死亡。 本实验中,三种广泛使用的内质网应激的诱导剂,包括衣霉素,DTT和MG132均引起了LC3-Ⅰ向LC3-Ⅱ的转化。该转化是细胞出现自噬的重要指标。同时,三种药物也导致mTOR的活性大幅度下降。而抑制自噬可以显著提高细胞在内质网应激下的存活率。已知TSC缺失的细胞中mTOR被组成型激活。而本实验表明,在内质网应激中,TSC缺失细胞的自噬水平显著低于其对照组细胞。由此可见,内质网应激导致的mTOR活性降低,是由于其对AKT/TSC/mTOR信号通路的下调所致。作为该通路中的两个重要调节蛋白,PTEN及AMPK并未参与该调控。4-PBA作为一种帮助蛋白质正确折叠的化学伴侣分子,部分恢复了由内质网应激下调的AKT/TSC/mTOR通路。 另外,根据相关文献报道,组成型激活的mTOR可导致内质网应激。本实验结果表明,由组成型激活的mTOR所导致的内质网应激,减弱了RTK/PI3K/AKT通路对多种生长因子的反应。同时,4-PBA可以恢复该反应。据此,本实验提出一种新的机制用以解释内质网应激引起的自噬,以及由mTOR到AKT的负反馈作用。
[Abstract]:Endoplasmic reticulum (ER) is an important organelle of eukaryotic cells. It is a place for protein synthesis, modification and folding. The disorder of endoplasmic reticulum balance caused by various reasons is called endoplasmic reticulum stress. Endoplasmic reticulum stress induces signal transduction from endoplasmic reticulum to cytoplasm and nucleus, which ultimately helps the cell to recover homeostasis and survive. However, severe endoplasmic reticulum stress can lead to autophagy and apoptosis. Little is known about the precise mechanism for regulating this process. This study suggests that endoplasmic reticulum stress induces autophagy and cell death by inhibiting mTOR pathway. In this study, three widely used endoplasmic reticulum (ER) stress inducers, including chlortetracycline DTT and MG132, caused the transformation of LC3- 鈪，
本文编号：2252910
[Abstract]:Endoplasmic reticulum (ER) is an important organelle of eukaryotic cells. It is a place for protein synthesis, modification and folding. The disorder of endoplasmic reticulum balance caused by various reasons is called endoplasmic reticulum stress. Endoplasmic reticulum stress induces signal transduction from endoplasmic reticulum to cytoplasm and nucleus, which ultimately helps the cell to recover homeostasis and survive. However, severe endoplasmic reticulum stress can lead to autophagy and apoptosis. Little is known about the precise mechanism for regulating this process. This study suggests that endoplasmic reticulum stress induces autophagy and cell death by inhibiting mTOR pathway. In this study, three widely used endoplasmic reticulum (ER) stress inducers, including chlortetracycline DTT and MG132, caused the transformation of LC3- 鈪，
本文编号：2252910
本文链接：https://www.wllwen.com/yixuelunwen/shiyanyixue/2252910.html
最近更新
教材专著
