PMID- 19054297
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20211203
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 46
IP  - 2
DP  - 2009 Mar
TI  - Melatonin attenuates methamphetamine-induced deactivation of the mammalian target 
      of rapamycin signaling to induce autophagy in SK-N-SH cells.
PG  - 199-206
LID - 10.1111/j.1600-079X.2008.00648.x [doi]
AB  - 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.
FAU - Kongsuphol, Patthara
AU  - Kongsuphol P
AD  - Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 
      Thailand.
FAU - Mukda, Sujira
AU  - Mukda S
FAU - Nopparat, Chutikorn
AU  - Nopparat C
FAU - Villarroel, Alfredo
AU  - Villarroel A
FAU - Govitrapong, Piyarat
AU  - Govitrapong P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081119
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antioxidants)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Phosphoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Antioxidants/pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Central Nervous System Stimulants/*pharmacology
MH  - Humans
MH  - Melatonin/*pharmacology
MH  - Methamphetamine/*pharmacology
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/12/05 09:00
MHDA- 2009/04/15 09:00
CRDT- 2008/12/05 09:00
PHST- 2008/12/05 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PHST- 2008/12/05 09:00 [entrez]
AID - JPI648 [pii]
AID - 10.1111/j.1600-079X.2008.00648.x [doi]
PST - ppublish
SO  - J Pineal Res. 2009 Mar;46(2):199-206. doi: 10.1111/j.1600-079X.2008.00648.x. Epub 
      2008 Nov 19.