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Purinergic receptor P2Y6 contributes to 1-methyl-4-phenylpyridinium-induced oxidative stress and cell death in neuronal SH-SY5Y cells.

Journal of neuroscience research | 2018

Oxidative stress and neural degeneration have been shown to be involved in the pathogenesis of Parkinson's disease (PD). The P2Y6 purinergic receptor (P2Y6R) has been shown to participate in the activation of microglia and the production of pro-inflammatory factors induced by lipopolysaccharide to cause neuronal loss. However, the function of P2Y6R during oxidative stress in neurons is unclear. In the present study, 1-methyl-4-phenylpyridinium (MPP+ ) treatment increased the level of UDP/P2Y6R on neuronal SH-SY5Y cells. Importantly, pharmacological inhibition of P2Y6R or knockdown of P2Y6R using a siRNA exerted an increased protective effect by preventing MPP+ -induced increases in the levels of reactive oxygen species (ROS), superoxide anion, inducible nitric oxide synthase (iNOS), and malondialdehyde (MDA) and down-regulation of superoxide dismutase 1 (SOD1) expression. UDP, an agonist of P2Y6R, enhanced the effects of MPP+ , which was also inhibited by apyrase or MRS2578. Additionally, P2Y6R knockdown also significantly reversed both the loss of cell viability and the increase in the levels of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and p38 (p-p38) caused by MPP+ stimulation. However, the inhibition of the ERK1/2 and p38 kinase signaling pathways had no effect on P2Y6R expression. Taken together, these results support the hypothesis that P2Y6R expressed on neuronal SH-SY5Y cell is associated with the progression of oxidative stress and cell death induced by MPP+ , suggesting that P2Y6R may play an important role in the pathogenesis of PD.

Pubmed ID: 28752899 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


P2Y6 antibody [EPR3816] (antibody)

RRID:AB_10562775

This monoclonal targets P2Y6 antibody [EPR3816]

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Superoxide Dismutase 1 antibody (antibody)

RRID:AB_302535

This polyclonal targets Superoxide Dismutase 1 antibody

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p44/42 MAPK (Erk1/2) Antibody (antibody)

RRID:AB_330744

This polyclonal targets p44/42 MAPK (Erk1/2)

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iNOS antibody (antibody)

RRID:AB_303872

This polyclonal targets iNOS antibody

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Phospho-SAPK/JNK (Thr183/Tyr185) Antibody (antibody)

RRID:AB_331659

This polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)

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SAPK/JNK Antibody (antibody)

RRID:AB_2250373

This polyclonal targets SAPK/JNK

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Phospho-p38 MAPK (Thr180/Tyr182) Antibody (antibody)

RRID:AB_331641

This polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)

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