Melatonin protects against rotenone-induced cell injury via inhibition of Omi and Bax-mediated autophagy in Hela cells
Article first published online: 25 AUG 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 52, Issue 1, pages 120–127, January 2012
How to Cite
Zhou, H., Chen, J., Lu, X., Shen, C., Zeng, J., Chen, L. and Pei, Z. (2012), Melatonin protects against rotenone-induced cell injury via inhibition of Omi and Bax-mediated autophagy in Hela cells. Journal of Pineal Research, 52: 120–127. doi: 10.1111/j.1600-079X.2011.00926.x
- Issue published online: 12 DEC 2011
- Article first published online: 25 AUG 2011
- Accepted manuscript online: 22 JUL 2011 11:42AM EST
- Received May 20, 2011; Accepted July 18, 2011.
Abstract: 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 μm) decreased cell survival of Hela cells in a dose-dependent manner. At concentrations ranging from 0.1 to 100 μm, 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 μm rotenone-induced autophagy. To determine whether melatonin would protect cells against rotenone-induced cell death and autophagy, we pretreated Hela cells with 250 μm 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 μm rotenone. Melatonin 250 μm treatment also suppressed cell death induced by 0.1–100 μm rotenone and protected against the formation of LC3-II in cells exposed to 1 μm rotenone. This work demonstrates a novel role for melatonin as a neuroprotective agent against rotenone.