PMID- 24326530
OWN - NLM
STAT- MEDLINE
DCOM- 20141007
LR  - 20220318
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 39
IP  - 2
DP  - 2014 Feb
TI  - 1-Methyl-4-phenylpyridinium-induced cell death via autophagy through a 
      Bcl-2/Beclin 1 complex-dependent pathway.
PG  - 225-32
LID - 10.1007/s11064-013-1208-8 [doi]
AB  - Several lines of evidence suggest that the mechanism underlying drug-induced 
      neuronal apoptosis is initiated by the increased production of reactive oxygen 
      species (ROS). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin, 
      has been shown to initiate an apoptotic cascade by increasing ROS in the 
      dopaminergic neurons of the substantia nigra, leading to the morphological and 
      physiological features associated with Parkinson's disease. Recently, it has been 
      reported that autophagy, a type of programmed cell death independent of the 
      apoptotic cascade, also plays a role in neuronal damage. Although autophagy is 
      negatively regulated by the mammalian target of rapamycin receptor (mTOR), there 
      is some evidence showing a novel function for the anti-apoptotic protein Bcl-2. 
      Bcl-2 is proposed to play a role in negatively regulating autophagy by blocking 
      an essential protein in the signaling pathway, Beclin 1. Nevertheless, it is 
      unclear whether autophagy is also correlated with apoptotic signaling in 
      1-methyl-4-phenylpyridinium (MPP(+)) toxicity. Therefore, we hypothesized that 
      the MPP(+) toxicity generally associated with initiating the apoptotic signaling 
      cascade also increases an autophagic phenotype in neuronal cells. Using the 
      SK-N-SH dopaminergic cell lines, we demonstrate that MPP(+) increases the 
      expression of microtubule-associated protein light chain 3 (LC3-II), an 
      autophagosome membrane marker and the mTOR signaling pathway, and Beclin 1 while 
      decreasing the Bcl-2 levels. Moreover, these expressions correlate with a 
      decreased binding ratio between Bcl-2 and Beclin 1, in effect limiting the 
      regulation of the downstream autophagic markers, such as LC3-II. Our results 
      indicate that MPP(+) can induce autophagy in SK-N-SH cells by decreasing the 
      Bcl-2/Beclin 1 complex.
FAU - Nopparat, Chutikorn
AU  - Nopparat C
AD  - Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol 
      University, Nakornpathom, Thailand.
FAU - Porter, James E
AU  - Porter JE
FAU - Ebadi, Manuchair
AU  - Ebadi M
FAU - Govitrapong, Piyarat
AU  - Govitrapong P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131211
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology
MH  - Apoptosis Regulatory Proteins
MH  - Autophagy/*drug effects
MH  - Beclin-1
MH  - Blotting, Western
MH  - Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Membrane Proteins
MH  - Oxidative Stress
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Substantia Nigra/cytology/drug effects/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2013/12/12 06:00
MHDA- 2014/10/08 06:00
CRDT- 2013/12/12 06:00
PHST- 2013/07/15 00:00 [received]
PHST- 2013/11/25 00:00 [accepted]
PHST- 2013/10/29 00:00 [revised]
PHST- 2013/12/12 06:00 [entrez]
PHST- 2013/12/12 06:00 [pubmed]
PHST- 2014/10/08 06:00 [medline]
AID - 10.1007/s11064-013-1208-8 [doi]
PST - ppublish
SO  - Neurochem Res. 2014 Feb;39(2):225-32. doi: 10.1007/s11064-013-1208-8. Epub 2013 
      Dec 11.