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Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium
Author(s) -
Kamdar O.,
Le Wei,
Zhang J.,
Ghio A.J.,
Rosen G.D.,
Upadhyay D.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.09.030
Subject(s) - apoptosis , oxidative stress , mitochondrion , cystic fibrosis , microbiology and biotechnology , reactive oxygen species , chemistry , respiratory epithelium , mitochondrial apoptosis induced channel , thenoyltrifluoroacetone , inner mitochondrial membrane , epithelium , mitochondrial ros , bcl 2 family , biology , biochemistry , programmed cell death , genetics , chromatography , solvent extraction , extraction (chemistry)
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.