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Melatonin protects against rotenone‐induced cell injury via inhibition of Omi and Bax‐mediated autophagy in Hela cells
Author(s) -
Zhou Hongyan,
Chen Jie,
Lu Xilin,
Shen Cunzhou,
Zeng Jinsheng,
Chen Ling,
Pei Zhong
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00926.x
Subject(s) - rotenone , melatonin , autophagy , programmed cell death , microbiology and biotechnology , biology , hela , pharmacology , cell , biochemistry , apoptosis , endocrinology , mitochondrion
Parkinson’s disease is the second most common neurodegenerative disease, and environmental toxins such as rotenone play an important role in causing degeneration of dopaminergic neurons. Melatonin, a major secretory product of pineal, is recently reported to protect against rotenone‐induced cell death in animal models. Yet, the mechanism involved in this protection needs to be elucidated. Here, we report that rotenone treatment (0–100 μ m ) decreased cell survival of Hela cells in a dose‐dependent manner. At concentrations ranging from 0.1 to 100 μ m , rotenone induced a dose‐dependent increase in the expression of microtubule‐associated protein 1 light chain 3 (LC3)‐II, a protein associated with the autophagosomal membrane. Knockdown of Bax or Omi using shRNA inhibited 1 μ m rotenone‐induced autophagy. To determine whether melatonin would protect cells against rotenone‐induced cell death and autophagy, we pretreated Hela cells with 250 μ m melatonin for 24 hr in the presence of rotenone. Melatonin inhibited Bax expression and the release of the omi/HtrA2 into the cytoplasm induced by 1 μ m rotenone. Melatonin 250 μ m treatment also suppressed cell death induced by 0.1–100 μ m rotenone and protected against the formation of LC3‐II in cells exposed to 1 μ m rotenone. This work demonstrates a novel role for melatonin as a neuroprotective agent against rotenone.