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In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in PC12 cells treated with diquat. We found that diquat induced apoptosis, as demonstrated by the activation of caspases and nuclear condensation, inhibition of mitochondrial complex I activity, and decreased ATP level in PC12 cells. Diquat also reduced the dopamine level, indicating that cell death induced by diquat is due to cytotoxicity of dopaminergic neuronal components in these cells. Exposure of PC12 cells to diquat led to the production of reactive oxygen species (ROS), and the antioxidant <jats:italic>N<\/jats:italic>\u2010acetyl\u2010cystein attenuated the cytotoxicity of caspase\u20103 pathways. These results demonstrate that diquat\u2010induced apoptosis is involved in mitochondrial dysfunction through production of ROS. Furthermore, diquat increased expression of cyclooxygenase\u20102 (COX\u20102) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) via inflammatory stimulation. Diquat induced nuclear accumulation of NF\u2010\u03baB and p53 proteins. Importantly, an inhibitor of NF\u2010\u03baB nuclear translocation blocked the increase of p53. Both NF\u2010\u03baB and p53 inhibitors also blocked the diquat\u2010induced inflammatory response. Pretreatment of cells with meloxicam, a COX\u20102 inhibitor, also blocked apoptosis and mitochondrial dysfunction. These results represent a unique molecular characterization of diquat\u2010induced cytotoxicity in PC12 cells. Our results demonstrate that diquat induces cell damage in part through inflammatory responses via NF\u2010\u03baB\u2010mediated p53 signaling. This suggests the potential to generate mitochondrial damage via inflammatory responses and inflammatory stimulation\u2010related neurodegenerative disease.<\/jats:p>","DOI":"10.1002\/tox.22552","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T07:32:36Z","timestamp":1519716756000},"page":"1005-1018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["NF\u2010\u03baB\/p53\u2010activated inflammatory response involves in diquat\u2010induced mitochondrial dysfunction and apoptosis"],"prefix":"10.1002","volume":"33","author":[{"given":"Su Eun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Pharmacology College of Medicine, Hanyang University  Seoul, Republic of Korea"},{"name":"Graduate School of Biomedical Science and Engineering Hanyang University  Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun 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