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- Title
AMPK mediates a pro-survival autophagy downstream of PARP-1 activation in response to DNA alkylating agents
- Authors
Zhou, Jing; Ng, Shukie; Huang, Qing; Wu, You-Tong; Li, Zhengqiu; Yao, Shao Q.; Shen, Han-Ming
- Abstract
Abstract: 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.
- Subjects
CYCLIC-AMP-dependent protein kinase; POLY(ADP-ribose) polymerase; DNA alkylation; AUTOPHAGY; ALKYLATING agents; MTOR protein; CELL death; ADENOSINE monophosphate
- Publication
FEBS Letters, 2013, Vol 587, Issue 2, p170
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2012.11.018