PMID- 19666105 OWN - NLM STAT- MEDLINE DCOM- 20100105 LR - 20220310 IS - 1873-4596 (Electronic) IS - 0891-5849 (Print) IS - 0891-5849 (Linking) VI - 47 IP - 8 DP - 2009 Oct 15 TI - Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. PG - 1221-9 LID - 10.1016/j.freeradbiomed.2009.08.001 [doi] AB - A reduction in endogenously generated reactive oxygen species in vivo delays benzo(a)pyrene (BaP)-accelerated atherosclerosis, as revealed in hypercholesterolemic mice overexpressing Cu/Zn-superoxide dismutase (SOD) and/or catalase. To understand the molecular events involved in this protective action, we studied the effects of Cu/Zn-SOD and/or catalase overexpression on BaP detoxification and on aryl hydrocarbon receptor (AhR) expression and its target gene expression in mouse aortic endothelial cells (MAECs). Our data demonstrate that overexpression of Cu/Zn-SOD and/or catalase leads to an 18- to 20-fold increase in the expression of AhR protein in MAECs. After BaP exposure, the amount of AhR binding to the cytochrome P450 (CYP) 1A1 promoter was significantly greater, and the concentrations of BaP reactive intermediates were significantly less in MAECs overexpressing Cu/Zn-SOD and/or catalase than in wild-type cells. In addition, the BaP-induced CYP1A1 and 1B1 protein levels and BaP-elevated glutathione S-transferase (GST) activity were significantly higher in these transgenic cells, in parallel with elevated GSTp1, CYP1A1, and CYP1B1 mRNA levels, compared to wild-type MAECs. Moreover, knockdown of AhR with RNA interference diminished the Cu/Zn-SOD and catalase enhancement of CYP1A1 expression, GST activity, and BaP detoxification. These data demonstrate that overexpression of Cu/Zn-SOD and/or catalase is associated with upregulation of AhR and its target genes, such as xenobiotic-metabolizing enzymes. FAU - Wang, Zefen AU - Wang Z AD - Department of Cardiovascular Biology, Meharry Medical College, Nashville, TN 37208, USA. FAU - Yang, Hong AU - Yang H FAU - Ramesh, Aramandla AU - Ramesh A FAU - Roberts, L Jackson 2nd AU - Roberts LJ 2nd FAU - Zhou, Lichun AU - Zhou L FAU - Lin, Xinhua AU - Lin X FAU - Zhao, Yanfeng AU - Zhao Y FAU - Guo, Zhongmao AU - Guo Z LA - eng GR - K01HL-076623/HL/NHLBI NIH HHS/United States GR - R01 ES014472-02/ES/NIEHS NIH HHS/United States GR - R03 CA130112/CA/NCI NIH HHS/United States GR - R01 ES014472-01A1/ES/NIEHS NIH HHS/United States GR - S11 ES014156/ES/NIEHS NIH HHS/United States GR - R03CA130112-01/CA/NCI NIH HHS/United States GR - G12 RR003032/RR/NCRR NIH HHS/United States GR - R01 ES014472/ES/NIEHS NIH HHS/United States GR - R01ES014471/ES/NIEHS NIH HHS/United States GR - S11ES014156-02/ES/NIEHS NIH HHS/United States GR - G12RR03032/RR/NCRR NIH HHS/United States GR - K01 HL076623/HL/NHLBI NIH HHS/United States GR - G12RR003032/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090807 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (F2-Isoprostanes) RN - 0 (Furans) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 3417WMA06D (Benzo(a)pyrene) RN - EC 1.11.1.6 (Catalase) RN - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases) RN - EC 1.14.14.1 (Cyp1b1 protein, mouse) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1B1) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Animals MH - Aorta/cytology/*metabolism MH - Aryl Hydrocarbon Hydroxylases/genetics/metabolism MH - Benzo(a)pyrene/*pharmacokinetics MH - Blotting, Western MH - Catalase/*metabolism MH - Cells, Cultured MH - Cytochrome P-450 CYP1A1/genetics/metabolism MH - Cytochrome P-450 CYP1B1 MH - Endothelium, Vascular/cytology/*metabolism MH - F2-Isoprostanes/metabolism MH - Furans/metabolism MH - Glutathione Transferase/genetics/metabolism MH - Inactivation, Metabolic MH - Mice MH - RNA, Messenger/genetics/metabolism MH - RNA, Small Interfering/pharmacology MH - Receptors, Aryl Hydrocarbon/antagonists & inhibitors/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Superoxide Dismutase/*metabolism MH - Up-Regulation PMC - PMC2846758 MID - NIHMS184486 EDAT- 2009/08/12 09:00 MHDA- 2010/01/06 06:00 PMCR- 2010/05/15 CRDT- 2009/08/12 09:00 PHST- 2009/06/22 00:00 [received] PHST- 2009/08/01 00:00 [accepted] PHST- 2009/08/12 09:00 [entrez] PHST- 2009/08/12 09:00 [pubmed] PHST- 2010/01/06 06:00 [medline] PHST- 2010/05/15 00:00 [pmc-release] AID - S0891-5849(09)00470-5 [pii] AID - 10.1016/j.freeradbiomed.2009.08.001 [doi] PST - ppublish SO - Free Radic Biol Med. 2009 Oct 15;47(8):1221-9. doi: 10.1016/j.freeradbiomed.2009.08.001. Epub 2009 Aug 7.