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AMPK mediates a pro‐survival autophagy downstream of PARP‐1 activation in response to DNA alkylating agents
Author(s) -
Zhou Jing,
Ng Shukie,
Huang Qing,
Wu You-Tong,
Li Zhengqiu,
Yao Shao Q.,
Shen Han-Ming
Publication year - 2013
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 - 10.1016/j.febslet.2012.11.018
Subject(s) - autophagy , ampk , microbiology and biotechnology , programmed cell death , poly adp ribose polymerase , pi3k/akt/mtor pathway , dna damage , chemistry , dna repair , biology , signal transduction , cancer research , apoptosis , dna , phosphorylation , protein kinase a , biochemistry , polymerase
In this study we aim to elucidate the signaling pathway and biological function of autophagy induced by MNNG, a commonly used DNA alkylating agent. We first observed that MNNG is able to induce necrotic cell death and autophagy in Bax−/− Bak−/− double knockout MEFs. We analyzed the critical role of PARP‐1 activation and ATP depletion in MNNG‐mediated cell death and autophagy via AMPK activation and mTOR suppression. We provide evidence that suppression of AMPK blocks MNNG‐induced autophagy and enhances cell death, suggesting the pro‐survival function of autophagy in MNNG‐treated cells. Taken together, data from this study reveal a novel mechanism in controlling MNNG‐mediated autophagy via AMPK activation downstream of PARP‐1 activation and ATP depletion.