title: AP-1 activation attenuates the arsenite-induced apoptotic response in human bronchial epithelial cells by up-regulating HO-1 expression.
abstract: Arsenite is a cytotoxic reagent that has been used clinically to treat certain cancers. Although the cytotoxic mechanisms of arsenite have been investigated, the cellular mechanisms that act against arsenite damage are poorly understood. Heme oxygenase 1 (HO-1) has been implicated in cellular survival under other multiple stress conditions. Here, we show that a significant induction of HO-1 expression is present in human bronchial epithelial cells (Beas-2B) treated with lethal doses of arsenite treatment. This induction depends on the known ERK/AP1 signaling pathway. As expected, HO-1 RNAi knockdown, or ERK/AP1 inhibition, renders the Beas-2B cells more sensitive to arsenite damage. Our data thus suggest that transcriptional upregulation of HO-1 expression via a putative ERK/AP-1 pathway constitutes an inherent mechanism by which arsenite-induced apoptosis is attenuated.
authors.affiliation: Department of New Drug Screening Center, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
authors.lastname: Aodengqimuge
authors.forename: Shasha
authors.initials: S
authors.lastname: Liu
authors.forename: Sanyue
authors.initials: S
authors.lastname: Mai
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Meiru
authors.initials: M
authors.lastname: Hu
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.forename: Lun
authors.initials: L
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D018053:Arsenites; D005419:Flavonoids; D018808:Transcription Factor AP-1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C015001:arsenite; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one