ATP depletion is the major cause of MPP+ induced dopamine neuronal death and worm lethality in alpha-synuclein transgenic C. elegans.
OBJECTIVE
To investigate the toxic effect of environmental neurotoxin MPP+ to C. elegans and identify the mechanisms that cause the toxicity.


METHODS
Human 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.


RESULTS
We 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.


CONCLUSIONS
MPP+ 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.
Wang
Yi-Min
YM
Neural Genomics Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Pu
Pu
P
Le
Wei-Dong
WD
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism* / Q000401:mortality; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051844:alpha-Synuclein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D006540:Herbicides; D051844:alpha-Synuclein; D000255:Adenosine Triphosphate; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine