title: Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.
abstract: We studied the effects of airborne particulate matters (PM) on cystic fibrosis (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via the modulation of Bcl family proteins in CF.
authors.affiliation: Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: O
authors.initials: O
authors.lastname: Kamdar
authors.forename: Wei
authors.initials: W
authors.lastname: Le
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: G D
authors.initials: GD
authors.lastname: Rosen
authors.forename: D
authors.initials: D
authors.lastname: Upadhyay
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000473:pathology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D052638:Particulate Matter