自噬
PI3K/AKT/mTOR通路
医学
磷酸化
急性胰腺炎
胰腺炎
内科学
癌症研究
细胞生物学
内分泌学
细胞凋亡
信号转导
化学
生物
生物化学
作者
Yangyang Hu,Chunhua Zhou,Wen-Huan Dou,Wen Tang,Chuang-Ying Hu,Duanmin Hu,Hui Feng,Jian-Zong Wang,Qian Ming-hui,Guangfeng Cheng,Shaofeng Wang
出处
期刊:Pancreatology
[Elsevier]
日期:2015-09-01
卷期号:15 (5): 470-477
被引量:12
标识
DOI:10.1016/j.pan.2015.06.004
摘要
Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms.AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity.AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury.Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.
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