Activation of autophagy through calcium-dependent AMPK/mTOR and PKCθ pathway causes activation of rat hepatic stellate cells under hypoxic stress
Activation of autophagy through calcium-dependent AMPK/mTOR and PKCθ pathway causes activation of rat hepatic stellate cells under hypoxic stress
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通过钙依赖性 AMPK/mTOR 和 PKC theta 途径激活自噬导致缺氧应激下大鼠肝星状细胞的激活
DOI：
10.1002/1873-3468.12090
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发表时间：
2016-03-01
期刊：
影响因子：
3.5
通讯作者：
Zhou, Mengtao
中科院分区：
文献类型：
--
作者：
Jin, Yuepeng;Bai, Yongyu;Zhou, Mengtao
肝星状细胞（hepatic stellate cells，HSC）的活化是肝纤维化的重要环节。然而，HSC如何在缺氧微环境中被激活仍不清楚。在这里，我们发现缺氧增加大鼠HSC的自噬。此外，缺氧诱导细胞内钙浓度（[Ca 2 +]（i））的升高，这是由胞质Ca 2+螯合剂或磷脂酶C（PLC）特异性抑制剂消除。此外，缺氧诱导的自噬涉及5 '-腺苷一磷酸激活的蛋白激酶（AMPK）-雷帕霉素哺乳动物靶标（mTOR）和蛋白激酶C-θ（PKCh）途径的钙依赖性激活。此外，缺氧介导的HSC活化依赖于自噬。我们的研究结果表明，自噬诱导通过钙依赖性AMPK-mTOR和PKCh途径可能会导致激活的HSC在缺氧应激。
The activation of hepatic stellate cells (HSCs) is a prominent event in liver fibrogenesis. However, how HSCs are activated in the hypoxic microenvironment remains unclear. Here, we found that hypoxia increased autophagy in rat HSCs. Moreover, hypoxia induced an elevation of the intracellular calcium concentration ([Ca2+](i)), which was abolished by the cytosolic Ca2+ chelator or the phospholipase C (PLC)-specific inhibitor. Furthermore, hypoxia-induced autophagy involved the calcium-dependent activation of the 5'-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and protein kinase C-theta (PKCh) pathways. In addition, hypoxia-mediated activation of HSCs depended on autophagy. Our results suggest that autophagy induction via the calcium-dependent AMPK-mTOR and PKCh pathways might lead to the activation of HSCs during hypoxic stress.