title: Melatonin protects against rotenone-induced cell injury via inhibition of Omi and Bax-mediated autophagy in Hela cells.
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.
authors: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Hongyan
authors: H
authors: Zhou
authors: Jie
authors: J
authors: Chen
authors: Xilin
authors: X
authors: Lu
authors: Cunzhou
authors: C
authors: Shen
authors: Jinsheng
authors: J
authors: Zeng
authors: Ling
authors: L
authors: Chen
authors: Zhong
authors: Z
authors: Pei
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012402:Rotenone / Q000037:antagonists & inhibitors* / Q000633:toxicity; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D020011:Protective Agents; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; D008550:Melatonin