ATP depletion is the major cause of MPP+ induced dopamine neuronal death and worm lethality in alpha-synuclein transgenic C. elegans.
- Author:
Yi-Min WANG
1
;
Pu PU
;
Wei-Dong LE
Author Information
- Publication Type:Journal Article
- MeSH: 1-Methyl-4-phenylpyridinium; toxicity; Adenosine Triphosphate; deficiency; metabolism; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; drug effects; metabolism; Cell Death; Disease Models, Animal; Dopamine; metabolism; Herbicides; toxicity; Humans; MPTP Poisoning; metabolism; mortality; Neurons; drug effects; metabolism; alpha-Synuclein; drug effects; genetics; metabolism
- From:Neuroscience Bulletin 2007;23(6):329-335
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the toxic effect of environmental neurotoxin MPP+ to C. elegans and identify the mechanisms that cause the toxicity.
METHODSHuman alpha-synuclein transgenic C. elegans was used as the animal model, the toxic effect of MPP+ to dopamine (DA) neurons and the lifespan of worms was tested. The worms were feed with OP50 to determine whether ATP increase can rescue the worm from toxicity. ATP level and aberrant protein accumulation were analyzed in the MPP+ treated worms with or without OP50 addition.
RESULTSWe found that MPP+ induced DA cell death and worm lethality, which could be prevented by OP50 treatment. OP50 exerted the protective effect by up-regulating ATP level, even though it also induced accumulation of alpha-synuclein. Despite the undefined role of protein aggregation to the cell death, our results showed that the toxicity of MPP+ was mainly caused by the ATP depletion in the alpha-synuclein transgenic C. elegans.
CONCLUSIONMPP+ could induce DA neuronal death and worm lethality in alpha-synuclein transgenic C. elegans; Compared with the aggregation of alpha-synuclein, the major cause of MPP+ toxicity appeared due to ATP depletion.
