PMID- 21569840
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20220310
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 51
IP  - 1
DP  - 2011 Jul 1
TI  - Nrf2-dependent induction of NQO1 in mouse aortic endothelial cells overexpressing 
      catalase.
PG  - 97-106
LID - 10.1016/j.freeradbiomed.2011.04.020 [doi]
AB  - Overexpression of catalase has been shown to accelerate benzo(a)pyrene (BaP) 
      detoxification in mouse aortic endothelial cells (MAECs). NAD(P)H:quinone 
      oxidoreductase-1 (NQO1) is an enzyme that catalyzes BaP-quinone detoxification. 
      Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor-2 
      (Nrf2) are transcription factors that control NQO1 expression. Here, we 
      investigated the effects of catalase overexpression on NQO1, Nrf2, and AhR 
      expression. The levels of NQO1 mRNA and protein were comparable in MAECs isolated 
      from wild-type and transgenic mice that overexpress human catalase (hCatTg). BaP 
      treatment increased NQO1 mRNA and protein levels in both groups, with a 
      significantly greater induction in hCatTg MAECs than in wild-type cells. 
      BaP-induced NQO1 promoter activity was dramatically higher in hCatTg MAECs than 
      in wild-type cells. Our data also showed that the basal level of AhR and the 
      BaP-induced level of Nrf2 were significantly higher in hCatTg MAECs than in 
      wild-type cells. Inhibition of specificity protein-1 (Sp1) binding to the AhR 
      promoter region by mithramycin A reversed the enhancing effect of catalase 
      overexpression on AhR expression. Knockdown of AhR by RNA interference diminished 
      BaP-induced expression of Nrf2 and NQO1. Knockdown of Nrf2 significantly 
      decreased NQO1 mRNA and protein levels in cells with or without BaP treatment. 
      NQO1 promoter activity was abrogated by mutation of the Nrf2-binding site in this 
      promoter. In contrast, mutation of the AhR-binding site in the NQO1 promoter did 
      not affect the promoter activity. These results suggest that catalase 
      overexpression upregulates BaP-induced NQO1 expression by enhancing the 
      Sp1-AhR-Nrf2 signaling cascade.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Lin, Xinghua
AU  - Lin X
AD  - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
FAU - Yang, Hong
AU  - Yang H
FAU - Zhou, LiChun
AU  - Zhou L
FAU - Guo, ZhongMao
AU  - Guo Z
LA  - eng
GR  - SC1HL101431/HL/NHLBI NIH HHS/United States
GR  - SC1 HL101431/HL/NHLBI NIH HHS/United States
GR  - R01 ES014472-04/ES/NIEHS NIH HHS/United States
GR  - R01HL089382/HL/NHLBI NIH HHS/United States
GR  - R01 HL089382/HL/NHLBI NIH HHS/United States
GR  - U54 MD007593/MD/NIMHD NIH HHS/United States
GR  - U54 RR026140/RR/NCRR NIH HHS/United States
GR  - R01 ES014472/ES/NIEHS NIH HHS/United States
GR  - R01ES014471/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110417
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Ahr protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Sp1 Transcription Factor)
RN  - 97666-60-9 (mithramycin A)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (Nqo1 protein, mouse)
RN  - NIJ123W41V (Plicamycin)
SB  - IM
MH  - Animals
MH  - Aorta/*metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/biosynthesis/genetics
MH  - Catalase/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - NAD(P)H Dehydrogenase (Quinone)/*biosynthesis/genetics
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Plicamycin/analogs & derivatives/pharmacology
MH  - Promoter Regions, Genetic/drug effects/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Aryl Hydrocarbon/biosynthesis/genetics
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/metabolism
PMC - PMC3109219
MID - NIHMS298665
EDAT- 2011/05/17 06:00
MHDA- 2011/12/20 06:00
PMCR- 2012/07/01
CRDT- 2011/05/17 06:00
PHST- 2010/10/12 00:00 [received]
PHST- 2011/03/28 00:00 [revised]
PHST- 2011/04/11 00:00 [accepted]
PHST- 2011/05/17 06:00 [entrez]
PHST- 2011/05/17 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - S0891-5849(11)00246-2 [pii]
AID - 10.1016/j.freeradbiomed.2011.04.020 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2011 Jul 1;51(1):97-106. doi: 
      10.1016/j.freeradbiomed.2011.04.020. Epub 2011 Apr 17.