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Overexpression of Cu/Zn‐SOD and/or catalase accelerates benzo(a)pyrene detoxification by up‐regulation of AhR
Author(s) -
Guo Zhongmao,
Wang Zefen,
Ramesh Aramandla,
Zhou Lichun,
Yang Hong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.688.2
Subject(s) - catalase , benzo(a)pyrene , aryl hydrocarbon receptor , superoxide dismutase , chemistry , cyp1b1 , gene knockdown , microbiology and biotechnology , glutathione , cytochrome p450 , antioxidant , dismutase , reactive oxygen species , biochemistry , enzyme , carcinogen , apoptosis , biology , gene , transcription factor
Overexpression of Cu/Zn‐superoxide dismutase (SOD) and/or catalase has been shown to delay benzo[a]pyrene (BaP)‐accelerated atherosclerosis in hypercholesterolemia mice. The goal of this study is to assess the effect of these antioxidant enzymes on the expression of aryl hydrocarbon receptor (AhR) and its target genes. We observed that the AhR protein level is 18‐20 fold higher in the aorta endothelial cells (MAECs) obtained from mice overexpressing Cu/Zn‐SOD and/or catalase than in those from wild‐type mice. Following BaP exposure, the BaP reactive intermediates accumulated in the transgenic cells are significantly less, while the BaP‐induced cytochrome P450 (CYP) protein levels, and BaP‐elevated glutathione S‐transferase (GST) activity are significantly higher in the transgenic cells, in parallel with elevated CYP1A1, CYP1B1 and GSTp1 mRNA levels, when compared to wild‐type MAECs. Moreover, knockdown of AhR with RNA interference inhibits BaP‐induced CYP and GST expression and suppresses BaP detoxification in MAECs. These findings imply that up‐regulation of AhR is a mechanism for the increased BaP detoxification by overexpressing Cu/Zn‐SOD and/or catalase, which contributes to understanding the inhibitory effect of these antioxidant enzymes on BaP‐accelerated atherosclerosis. NIH grant support: RR003032 and K01HL‐076623 (H.Y.); R01ES014471 (Z.G.).