title: Sodium arsenite induces cyclooxygenase-2 expression in human uroepithelial cells through MAPK pathway activation and reactive oxygen species induction.
abstract: Arsenic can induce reactive oxygen species (ROS) leading to oxidative stress and carcinogenesis. Bladder is one of the major target organs of arsenic, and cyclooxygenase-2 (COX-2) may play an important role in arsenic-induced bladder cancer. However, the mechanism by which arsenic induces COX-2 in bladder cells remains unclear. This study aimed at investigating arsenic-mediated intracellular redox status and signaling cascades leading to COX-2 induction in human uroepithelial cells (SV-HUC-1). SV-HUC-1 cells were exposed to sodium arsenite and COX-2 expression, mitogen-activated protein kinase (MAPK) phosphorylation, glutathione (GSH) levels, ROS induction and Nrf2 expression were quantified. Our results demonstrate that arsenite (1-10 μM) elevates COX-2 expression, GSH levels, ROS and Nrf2 expression. Arsenite treatment for 24h stimulates phosphorylation of ERK and p38, but not JNK in SV-HUC-1 cells. Induction of Cox-2 mRNA levels by arsenite was attenuated by inhibitors of ERK, p38 and JNK. Arsenite-induced ROS generation and COX-2 expression were significantly attenuated by treatment with melatonin (a ROS scavenger), but enhanced by DL-buthionine-(S, R)-sulfoximine (BSO, an inhibitor of gamma-glutamylcysteine synthetase (γ-GCS) resulting in lower GSH and increased ROS levels). These data indicate that arsenite promotes an induction of ROS, which results in an induction of COX-2 expression through activation of the MAPK pathway.
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors: Huihui
authors: H
authors: Wang
authors: Shuhua
authors: S
authors: Xi
authors: Yuanyuan
authors: Y
authors: Xu
authors: Fei
authors: F
authors: Wang
authors: Yi
authors: Y
authors: Zheng
authors: Bing
authors: B
authors: Li
authors: Xin
authors: X
authors: Li
authors: Quanmei
authors: Q
authors: Zheng
authors: Guifan
authors: G
authors: Sun
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D019459:Urothelium / Q000166:cytology*
chemical_list: D018053:Arsenites; D002273:Carcinogens; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione