Journal
JOURNAL OF NEUROCHEMISTRY
Volume 120, Issue 2, Pages 279-291Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2011.07570.x
Keywords
apoptosis; L-PGDS; paraquat; SH-SY5Y cells
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21570151, 23116516]
- Research Foundation for Pharmaceutical Sciences
- Takeda Science Foundation
- Japan Foundation for Applied Enzymology
- Japan Society for the Promotion of Science
- Per Wrestling Foundation
- Grants-in-Aid for Scientific Research [10J10372, 21200076, 21570151, 21500428] Funding Source: KAKEN
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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 Parkinsons 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-?B 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-?B element. Thus, L-PGDS might potentially serve as an agent for prevention of human neurodegenerative diseases caused by oxidative stress and apoptosis.
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