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.

Abbreviations: AEC, alveolar epithelial cells, BAD, Bcl2-antagonist of cell death, CF, cystic fibrosis, CFTR, cystic fibrosis transmembrane conductance regulator, DIDS, 4,4′-diisothiocyanatostilbene-2,2′disulfonic acid, NHBE, normal human bronchial epithelial cells, PM, particulate matter, ROS, reactive oxygen species, TTFA, thenoyltrifluoroacetone

Keywords: Ambient air pollution particle, Apoptosis, Cystic fibrosis, Mitochondria, Particulate matter, Oxidative stress