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Activation of autophagy through calcium‐dependent AMPK / mTOR and PKC θ pathway causes activation of rat hepatic stellate cells under hypoxic stress
Author(s) -
Jin Yuepeng,
Bai Yongyu,
Ni Haizhen,
Qiang Li,
Ye Lechi,
Shan Yunfeng,
Zhou Mengtao
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12090
Subject(s) - autophagy , ampk , microbiology and biotechnology , pi3k/akt/mtor pathway , hepatic stellate cell , chemistry , cytosol , protein kinase a , protein kinase c , amp activated protein kinase , bag3 , mechanistic target of rapamycin , signal transduction , phosphorylation , biology , biochemistry , endocrinology , apoptosis , enzyme
The activation of hepatic stellate cells ( HSC s) is a prominent event in liver fibrogenesis. However, how HSC s are activated in the hypoxic microenvironment remains unclear. Here, we found that hypoxia increased autophagy in rat HSC s. Moreover, hypoxia induced an elevation of the intracellular calcium concentration ([Ca 2+ ] i ), which was abolished by the cytosolic Ca 2+ chelator or the phospholipase C ( PLC )‐specific inhibitor. Furthermore, hypoxia‐induced autophagy involved the calcium‐dependent activation of the 5ʹ‐adenosine monophosphate‐activated protein kinase ( AMPK )–mammalian target of rapamycin ( mTOR ) and protein kinase C‐theta ( PKC θ) pathways. In addition, hypoxia‐mediated activation of HSC s depended on autophagy. Our results suggest that autophagy induction via the calcium‐dependent AMPK – mTOR and PKC θ pathways might lead to the activation of HSC s during hypoxic stress.