Prevention of paraquat-induced apoptosis in human neuronal SH-SY5Y cells by lipocalin-type prostaglandin D synthase

J Neurochem. 2012 Jan;120(2):279-91. doi: 10.1111/j.1471-4159.2011.07570.x. Epub 2011 Nov 24.


Paraquat is a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-pyridine and acts as a potential etiologic factor for the development of Parkinson's disease. In this study, we investigated the protective roles of lipocalin-type prostaglandin (PG) D synthase (L-PGDS) against paraquat-mediated apoptosis of human neuronal SH-SY5Y cells. The treatment of SH-SY5Y cells with paraquat decreased the intracellular GSH level, and enhanced the cell death with elevation of the caspase activities. L-PGDS was expressed in SH-SY5Y cells, and its expression was enhanced with the peak at 2 h after the initiation of the treatment with paraquat. Inhibition of PGD₂ synthesis and exogenously added PGs showed no effects regarding the paraquat-mediated apoptosis. SiRNA-mediated suppression of L-PGDS expression in the paraquat-treated cells increased the cell death and caspase activities. Moreover, over-expression of L-PGDS suppressed the cell death and caspase activities in the paraquat-treated cells. The results of a promoter-luciferase assay demonstrated that paraquat-mediated elevation of L-PGDS gene expression occurred through the NF-κB element in the proximal promoter region of the L-PGDS gene in SH-SY5Y cells. These results indicate that L-PGDS protected against the apoptosis in the paraquat-treated SH-SY5Y cells through the up-regulation of L-PGDS expression via the NF-κB element. Thus, L-PGDS might potentially serve as an agent for prevention of human neurodegenerative diseases caused by oxidative stress and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromatin Immunoprecipitation
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glutathione / metabolism
  • Humans
  • Intramolecular Oxidoreductases / metabolism*
  • L-Lactate Dehydrogenase / metabolism
  • Lipocalins / metabolism*
  • NF-kappa B / metabolism
  • Neuroblastoma
  • Paraquat / toxicity*
  • Prostaglandin D2 / metabolism
  • Protein Binding / drug effects
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / pharmacology
  • Statistics, Nonparametric


  • Enzyme Inhibitors
  • Lipocalins
  • NF-kappa B
  • RNA, Small Interfering
  • L-Lactate Dehydrogenase
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • Glutathione
  • Paraquat
  • Prostaglandin D2