Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the me...Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 （HO-1） expression, which conferred protection against MPP^＋ -induced cytotoxici- ty, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP ＋ induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP^＋ -induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 ex- pression , and contribute to shed some light on the mechanisms whereby PB inhibit the MPP^＋ -induced neurotoxici- ty. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.展开更多
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Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 （HO-1） expression, which conferred protection against MPP^＋ -induced cytotoxici- ty, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP ＋ induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP^＋ -induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 ex- pression , and contribute to shed some light on the mechanisms whereby PB inhibit the MPP^＋ -induced neurotoxici- ty. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.
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.
