Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-synuclein transgenic C.elegans was used as the animal model...Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-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 ofα-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 theα-synuclein transgenic C.elegans.Conclusion MPP^＋ could induce DA neuronal death and worm lethality inα-synuclein transgenic C.elegans;Compared with the aggregation ofα-synuclein,the major cause of MPP^＋ toxicity appeared due to ATP depletion.展开更多
文摘Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-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 ofα-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 theα-synuclein transgenic C.elegans.Conclusion MPP^＋ could induce DA neuronal death and worm lethality inα-synuclein transgenic C.elegans;Compared with the aggregation ofα-synuclein,the major cause of MPP^＋ toxicity appeared due to ATP depletion.
