PMID- 20851755 OWN - NLM STAT- MEDLINE DCOM- 20101217 LR - 20161125 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 199 IP - 3 DP - 2010 Dec 15 TI - Paraquat induces cyclooxygenase-2 (COX-2) implicated toxicity in human neuroblastoma SH-SY5Y cells. PG - 239-46 LID - 10.1016/j.toxlet.2010.09.005 [doi] AB - Paraquat produces dopaminergic pathologies of Parkinson's disease, in which cyclooxygenase-2 (COX-2) is implicated. However, it is unclear whether paraquat induces toxicity within dopaminergic neurons through COX-2. To address this, human neuroblastoma SH-SY5Y cells were treated with paraquat and then the involving mechanism of COX-2 was investigated. We initially examined the involvement of COX-2 in paraquat-induced toxicity. Data suggest that COX-2 is implicated in paraquat-induced reduction of viability in SY5Y cells. Then, to confirm the presence of COX-2 in SY5Y cells, we examined COX-2 mRNA and protein levels, which are regulated by NF-kappaB. Data indicate that paraquat activates NF-kappaB and up-regulates COX-2. We then checked quinone-bound proteins as quinones produced by COX-2 bind to intracellular proteins. Paraquat obviously forms quinone-bound proteins, in particular, quinone-bound DJ-1 and this formation is attenuated by meloxicam. Finally, we investigated antioxidant system including nuclear factor erythroid-related factor 2 (Nrf2), gamma glutamylcysteine synthetase (gammaGCS), and glutathione (GSH) as DJ-1 is linked to Nrf2 and Nrf2 regulates gammaGCS expression and gammaGCS is a GSH synthesis enzyme. Paraquat decreases protein levels of Nrf2 and gammaGCS and intracellular GSH level and these decreases are alleviated by meloxicam. Therefore, collectively, our data indicate that paraquat induces COX-2 implicated toxicity in SY5Y cells. In conclusion, current findings support the idea that paraquat might produce toxicity in dopaminergic neurons through COX-2. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Yang, Wonsuk AU - Yang W AD - Inam Neuroscience Research Center, Department of Neurology, Sanbon Medical Center, College of Medicine, Wonkwang University, Sanbon, 435-040, Republic of Korea. FAU - Tiffany-Castiglioni, Evelyn AU - Tiffany-Castiglioni E FAU - Lee, Mi-Young AU - Lee MY FAU - Son, Il-Hong AU - Son IH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100921 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Herbicides) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (NFE2L2 protein, human) RN - 0 (Oncogene Proteins) RN - 0 (Quinones) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.1.2.- (PARK7 protein, human) RN - EC 3.1.2.- (Protein Deglycase DJ-1) RN - EC 6.3.2.2 (Glutamate-Cysteine Ligase) RN - GAN16C9B8O (Glutathione) RN - PLG39H7695 (Paraquat) SB - IM MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cyclooxygenase 2/analysis/genetics/*physiology MH - Glutamate-Cysteine Ligase/metabolism MH - Glutathione/analysis MH - Herbicides/*toxicity MH - Humans MH - Intracellular Signaling Peptides and Proteins/analysis/metabolism MH - L-Lactate Dehydrogenase/metabolism MH - NF-E2-Related Factor 2/metabolism MH - NF-kappa B/metabolism MH - Neuroblastoma/pathology MH - Oncogene Proteins/analysis/metabolism MH - Paraquat/*toxicity MH - Protein Deglycase DJ-1 MH - Quinones/metabolism EDAT- 2010/09/21 06:00 MHDA- 2010/12/18 06:00 CRDT- 2010/09/21 06:00 PHST- 2010/06/11 00:00 [received] PHST- 2010/07/15 00:00 [revised] PHST- 2010/09/08 00:00 [accepted] PHST- 2010/09/21 06:00 [entrez] PHST- 2010/09/21 06:00 [pubmed] PHST- 2010/12/18 06:00 [medline] AID - S0378-4274(10)01680-2 [pii] AID - 10.1016/j.toxlet.2010.09.005 [doi] PST - ppublish SO - Toxicol Lett. 2010 Dec 15;199(3):239-46. doi: 10.1016/j.toxlet.2010.09.005. Epub 2010 Sep 21.