title: Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells.
abstract: Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT1R) subtypes, AT1AR and AT1BR, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT1R subtypes, AT1AR and AT1BR following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT1R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT1R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT1R expression, thus highlighting a role of arsenic-induced aberrant AT1R signaling in the pathogenesis of hypertension.
authors.affiliation: Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Ekhtear
authors.initials: E
authors.lastname: Hossain
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ota
authors.forename: Miyuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Sivasundaram
authors.initials: S
authors.lastname: Karnan
authors.forename: Lkhagvasuren
authors.initials: L
authors.lastname: Damdindorj
authors.forename: Yuko
authors.initials: Y
authors.lastname: Konishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D018053:Arsenites / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D018053:Arsenites; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D017670:Sodium Compounds; C432165:pyrazolanthrone; C017947:sodium arsenite; D000111:Acetylcysteine