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Prevention of paraquat‐induced apoptosis in human neuronal SH‐SY5Y cells by lipocalin‐type prostaglandin D synthase
Author(s) -
Fujimori Ko,
Fukuhara Ayano,
Inui Takashi,
Allhorn Maria
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07570.x
Subject(s) - paraquat , apoptosis , sh sy5y , programmed cell death , biology , microbiology and biotechnology , oxidative stress , chemistry , cell culture , endocrinology , biochemistry , neuroblastoma , genetics
J. Neurochem. (2012) 120 , 279–291. 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 PGD 2 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.