title: Prevention of paraquat-induced apoptosis in human neuronal SH-SY5Y cells by lipocalin-type prostaglandin D synthase.
abstract: 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.
authors: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, Japan. fujimori@gly.oups.ac.jp
authors: Ko
authors: K
authors: Fujimori
authors: Ayano
authors: A
authors: Fukuhara
authors: Takashi
authors: T
authors: Inui
authors: Maria
authors: M
authors: Allhorn
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma; D010269:Paraquat / Q000633:toxicity*; D015230:Prostaglandin D2 / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D018709:Statistics, Nonparametric
chemical_list: D004791:Enzyme Inhibitors; D054834:Lipocalins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D005978:Glutathione; D010269:Paraquat; D015230:Prostaglandin D2