title: Oxidative stress and MAPK involved into ATF2 expression in immortalized human urothelial cells treated by arsenic.
abstract: ATF2 is a subfamily member of AP-1 and has an important role in cellular stress responses. ATF2 has been implicated in a transcriptional response leading to cell migration and malignant tumor progression. However, little is known about the effect of arsenic on expression of ATF2 and regulatory pathways in human urothelial cells. In this study, ATF2 expression was measured in NaAsO(2)-treated human uroepithelial cell line (SV-HUC-1) with 1, 2, 4, 8 and 10 μM concentrations in order to provide some basis data for the study on mechanism of bladder cancer induced by arsenic. We found that ATF2 expression levels at 2, 4, 8 and 10 μM arsenic-treated cells were significantly higher than those of control cells, and the strongest expression occurred in 4 μM NaAsO(2)-treated cells. Antioxidants (melatonin) and JNK or p38 inhibitors decreased significantly arsenic-induced ATF2 expression. Taken together, these data indicated that the increasing of ATF2 expression is mediated via oxidative stress induced by arsenic in SV-HUC-1 cells, and JNK or p38 rather than ERK is responsible for arsenic-induced ATF2 expression. ROS were also involved in arsenic induced the activation of JNK and p38 MAPK signaling pathway.
authors.affiliation: Department of Environmental and Occupational Health, Liaoning Provincial Key Laboratory of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, District of Heping, North Er Road, No. 92, Shenyang City 110001, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yingli
authors.initials: Y
authors.lastname: Song
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xi
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D018053:Arsenites / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D019459:Urothelium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000975:Antioxidants; D018053:Arsenites; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases