Sodium Arsenite Induces Cyclooxygenase-2 Expression in Human Uroepithelial Cells through MAPK Pathway Activation and Reactive Oxygen Species Induction.

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Sodium Arsenite Induces Cyclooxygenase-2 Expression in Human Uroepithelial Cells through MAPK Pathway Activation and Reactive Oxygen Species Induction.

Toxicol In Vitro. 2013 Jan 30;

Authors: Wang H, Xi S, Xu Y, Wang F, Zheng Y, Li B, Li X, Zheng Q, Sun G

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 ?M) elevates COX-2 expression, GSH levels, ROS and Nrf2 expression. Arsenite treatment for 24 h 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 (?-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.

PMID: 23376440 [PubMed - as supplied by publisher]

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