کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2599530 | 1133214 | 2012 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Induction of carbonyl reductase 1 (CBR1) expression in human lung tissues and lung cancer cells by the cigarette smoke constituent benzo[a]pyrene Induction of carbonyl reductase 1 (CBR1) expression in human lung tissues and lung cancer cells by the cigarette smoke constituent benzo[a]pyrene](/preview/png/2599530.png)
Carbonyl reductase 1 (CBR1) reduces various xenobiotic carbonyl substrates to corresponding alcohol metabolites. Here we demonstrated that benzo[a]pyrene (B[a]P), a potent pro-carcinogen and predominant polycyclic aromatic hydrocarbon (PAH) compound in cigarette smoke and air pollutants, upregulates CBR1 gene expression in vitro and in vivo, and that a proximal xenobiotic response element (XRE) motif (−122XRE) mediates the induction effect of B[a]P. First, we observed 46% and 50% increases in CBR1 mRNA and CBR1 protein levels, respectively, in human lung tissue samples from smokers compared to never-smokers. Second, we detected 3.0-fold (p < 0.0001) induction of CBR1 mRNA and 1.5-fold (p < 0.01) induction of CBR1 protein levels in cells of the human lung cancer cell line A549 incubated with 2.5 μM B[a]P for 24 h. Third, results from experiments with CBR1 promoter constructs indicated that a proximal XRE motif (−122XRE) mediates induction of reporter activity in response to B[a]P. Furthermore, we detected enhanced nuclear translocation of aryl hydrocarbon receptor (AhR) following B[a]P exposure in A549 cells. Finally, we demonstrated increased binding of specific protein complexes to −122XRE in nuclear extracts from B[a]P-treated cells and the presence of the AhR/Arnt complex in the specific nuclear protein −122XRE complexes.
► Carbonyl reductase 1 (CBR1) reduces a wide range of xenobiotic carbonyl substrates.
► CBR1 mRNA levels were higher in lungs from smokers than in samples from never-smokers.
► The smoke carcinogen benzo[a]pyrene (B[a]P) induces CBR1 expression in A549 cells.
► B[a]P increases binding of protein complexes to a xenobiotic response element (XRE).
Journal: Toxicology Letters - Volume 211, Issue 3, 20 June 2012, Pages 266–273