Paraquat induces cyclooxygenase-2 (COX-2) implicated toxicity in human neuroblastoma SH-SY5Y cells.
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-κB. Data indicate that paraquat activates NF-κB 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 (γGCS), and glutathione (GSH) as DJ-1 is linked to Nrf2 and Nrf2 regulates γGCS expression and γGCS is a GSH synthesis enzyme. Paraquat decreases protein levels of Nrf2 and γGCS 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.
Yang
Wonsuk
W
Inam Neuroscience Research Center, Department of Neurology, Sanbon Medical Center, College of Medicine, Wonkwang University, Sanbon, 435-040, Republic of Korea.
Tiffany-Castiglioni
Evelyn
E
Lee
Mi-Young
MY
Son
Il-Hong
IH
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D015513:Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D000071617:Protein Deglycase DJ-1; D011809:Quinones / Q000378:metabolism
D006540:Herbicides; D047908:Intracellular Signaling Peptides and Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D015513:Oncogene Proteins; D011809:Quinones; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D010269:Paraquat