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

Fujimori, Ko; Fukuhara, Ayano; Inui, Takashi and Allhorn, Maria LU (2012) In Journal of Neurochemistry 120. p.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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurochemistry
volume
120
pages
279 - 291
publisher
Wiley-Blackwell
external identifiers
  • wos:000298601400010
  • pmid:22043816
  • scopus:84155172357
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2011.07570.x
language
English
LU publication?
yes
id
17b7a2ba-cfd0-4ada-9d20-04dddc0853cb (old id 2221340)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22043816?dopt=Abstract
date added to LUP
2011-12-02 18:20:44
date last changed
2017-05-21 04:38:30
@article{17b7a2ba-cfd0-4ada-9d20-04dddc0853cb,
  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.},
  author       = {Fujimori, Ko and Fukuhara, Ayano and Inui, Takashi and Allhorn, Maria},
  issn         = {1471-4159},
  language     = {eng},
  pages        = {279--291},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Prevention of paraquat-induced apoptosis in human neuronal SH-SY5Y cells by lipocalin-type prostaglandin D synthase.},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2011.07570.x},
  volume       = {120},
  year         = {2012},
}