Publication: Melatonin attenuates methamphetamine-induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK-N-SH cells
Issued Date
2009-03-01
Resource Type
ISSN
1600079X
07423098
07423098
Other identifier(s)
2-s2.0-59149091414
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Pineal Research. Vol.46, No.2 (2009), 199-206
Suggested Citation
Patthara Kongsuphol, Sujira Mukda, Chutikorn Nopparat, Alfredo Villarroel, Piyarat Govitrapong Melatonin attenuates methamphetamine-induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK-N-SH cells. Journal of Pineal Research. Vol.46, No.2 (2009), 199-206. doi:10.1111/j.1600-079X.2008.00648.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27272
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Title
Melatonin attenuates methamphetamine-induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK-N-SH cells
Abstract
Methamphetamine (METH) is a commonly abused drug that damages nerve terminals by causing reactive oxygen species (ROS) formation, apoptosis, and neuronal damage. Autophagy, a type of programmed cell death independent of apoptosis, is negatively regulated by the mammalian target of the rapamycin (mTOR) signaling pathway. It is not known, however, whether autophagy is involved in METH-induced neurotoxicity. Therefore, we investigated the effect of METH on autophagy and its upstream regulator, the mTOR signaling pathway. Using the SK-N-SH dopaminergic cell line, we found that METH induces the expression of LC3-II, a protein associated with the autophagosome membrane, in a dose-dependent manner. Moreover, METH inhibits the phosphorylation of mTOR and the action of its downstream target, the eukaryotic initiation factor (eIF)4E-binding protein, 4EBP1. Melatonin, a major secretory product of pineal, is a potent naturally produced antioxidant that acts through various mechanisms to ameliorate the toxic effects of ROS. We found that a pretreatment with melatonin enhances mTOR activity and 4EBP1 phosphorylation and protects against the formation of LC3-II in SK-N-SH cells exposed to METH. This work demonstrates a novel role for melatonin as a neuroprotective agent against METH. © 2008 The Authors.