title: Manganese activates caspase-9-dependent apoptosis in human bronchial epithelial cells.
abstract: Acute inhalation exposure to high levels of manganese (Mn) is associated with pulmonary edema and impaired function. The immune-mediated lung epithelium injury of Mn in vivo and in vitro experiments has been well characterized, whereas its apoptotic effect is not well defined. Our results show that human bronchial epithelial (16HBE) cells undergo caspase-9-mediated cell death in response to Mn. Loss of mitochondrial membrane potential (ΔΨm), the formation of reactive oxygen species and release of cytochrome c were regulated during this process. In addition, decreasing c-Myc level and increasing of phosphorylated p53 (Ser 15) and WAF1/p21 were also taken part in Mn-mediated lung toxicity. Proteasome inhibitor MG132 could increase c-Myc protein in abundance. Taking together, our results demonstrate that caspase-9-dependent intrinsic pathway, the downregulation of c-Myc and the upregulation of p53 and phosphorylated p53 might be responsible for Mn-mediated apoptosis in 16HBE cells. Moreover, c-Myc decrease might be due to increased degradation through the ubiquitin-proteasome pathway.
authors.affiliation: 1Department of Prevention, Tongji University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Sang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology*; D053453:Caspase 9 / Q000378:metabolism*; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D008345:Manganese; D053453:Caspase 9