Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.
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.
Kamdar
O
O
Stanford University School of Medicine, Stanford, CA 94305, USA.
Le
Wei
W
Zhang
J
J
Ghio
A J
AJ
Rosen
G D
GD
Upadhyay
D
D
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
D051017:Apoptosis Regulatory Proteins; D052638:Particulate Matter