title: Nuclear translocation of nuclear factor kappa B is regulated by G protein signaling pathway in arsenite-induced apoptosis in HBE cell line.
abstract: Arsenite is a certainly apoptosis inducer in various cell types. However, the detailed mechanism underlying how arsenite trigger apoptosis remains elusive. In this study, using human bronchial epithelial cell as a culture system, we demonstrated that arsenite-induced nuclear translocation of nuclear factor kappa B (NF-κB) resulted in the release of cytochrome c, the modulation of Fas and FasL, caspase activation, and ultimately leading to cell apoptosis. Importantly, we showed for the first time that the NF-κB-mediated apoptosis induced by arsenite was regulated by G protein-adenylate cyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. Inhibition of this classical G protein signaling pathway by a typical PKA inhibitor, H-89, caused the inactivation of NF-κB, the depletion of caspase-3, 8 and 9 activities, and thus reducing the level of cell apoptosis. Taken together, our results indicate that arsenite is able to trigger cell apoptosis in human bronchial epithelial cells through the nuclear translocation of NF-κB, which can be modulated by G protein signaling pathway. These findings further suggest that inhibition of G protein-mediated pathway by specific inhibitors may be a potential strategy for the prevention of arsenite toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1819-1833, 2016.
authors: Department of Occupational and Environmental Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.|Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Chengzhi
authors: C
authors: Chen
authors: Department of Occupational and Environmental Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Shiyan
authors: S
authors: Gu
authors: Department of Occupational and Environmental Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.|Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Xuejun
authors: X
authors: Jiang
authors: Department of Occupational and Environmental Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Zunzhen
authors: Z
authors: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000262:Adenylyl Cyclases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014873:Water Pollutants / Q000633:toxicity*
chemical_list: D018053:Arsenites; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D014873:Water Pollutants; C015482:protein kinase modulator; D045304:Cytochromes c; D000242:Cyclic AMP; D020169:Caspases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C015001:arsenite
keywords: G protein; NF-κB; apoptosis; arsenite; signal transduction