PMID- 11008122
OWN - NLM
STAT- MEDLINE
DCOM- 20001107
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 60
IP  - 9
DP  - 2000 Nov 1
TI  - Profiles of antioxidant/electrophile response element (ARE/EpRE) nuclear protein 
      binding and c-Ha-ras transactivation in vascular smooth muscle cells treated with 
      oxidative metabolites of benzo[a]pyrene.
PG  - 1285-96
AB  - Activation of nuclear protein binding to the antioxidant/electrophile response 
      element (ARE/EpRE) by benzo[a]pyrene (BaP) in vascular smooth muscle cells 
      (vSMCs) is associated with transcriptional deregulation of c-Ha-ras. This 
      response may be mediated by oxidative intermediates of BaP generated during the 
      course of cellular metabolism. To test this hypothesis, the profile of ARE/EpRE 
      protein binding and transactivation elicited by BaP was compared with that of 
      3-hydroxy BaP (3-OH BaP) (0.03 to 3.0 microM), BaP 7,8-dihydrodiol (BaP 7,8-diol) 
      (0.03 to 3.0 microM), BaP 3,6-quinone (BaP 3,6-Q) (0.0003 to 3.0 microM), and 
      H(2)O(2) (25 to 100 microM). Specific protein binding to the consensus c-Ha-ras 
      ARE/EpRE was observed in vSMCs treated with all BaP metabolites at concentrations 
      considerably lower than those required for the parent compound. H(2)O(2), a 
      by-product of BaP 3,6-Q redox cycling, also increased binding to the ARE/EpRE. 
      Treatment of vSMCs with oxidative BaP metabolites or H(2)O(2) transactivated the 
      c-Ha-ras promoter in all instances, but the response was consistently half of the 
      maximal induction elicited by BaP. Similar proteins cross-linked specifically to 
      the consensus c-Ha-ras ARE/EpRE sequence in cells treated with BaP or its 
      oxidative intermediates. The protein binding profile in the c-Ha-ras promoter was 
      similar to that in the NADPH:quinone reductase gene (NQO(1)) and the glutathione 
      S-transferase Ya gene (GSTYa) promoters, but the relative abundance of individual 
      complexes was promoter-specific. We conclude that oxidative intermediates of BaP 
      mediate activation of nuclear protein binding to ARE/EpRE and contribute to 
      transcriptional de-regulation of c-Ha-ras in vSMCs.
FAU - Miller, K P
AU  - Miller KP
AD  - Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas 
      A&M University, College Station, TX 77843-4466, USA.
FAU - Chen, Y H
AU  - Chen YH
FAU - Hastings, V L
AU  - Hastings VL
FAU - Bral, C M
AU  - Bral CM
FAU - Ramos, K S
AU  - Ramos KS
LA  - eng
GR  - 4849/PHS HHS/United States
GR  - ES 09106/ES/NIEHS NIH HHS/United States
GR  - T32 ES 07273/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antioxidants)
RN  - 0 (Nuclear Proteins)
RN  - 3417WMA06D (Benzo(a)pyrene)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Benzo(a)pyrene/metabolism/*pharmacology
MH  - Female
MH  - Genes, ras/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Smooth, Vascular/*drug effects/physiology
MH  - Nuclear Proteins/*metabolism
MH  - Oxidative Stress/physiology
MH  - Promoter Regions, Genetic/physiology
MH  - Protein Binding
MH  - Transcriptional Activation/*drug effects
EDAT- 2000/09/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/29 11:00
PHST- 2000/09/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/29 11:00 [entrez]
AID - S0006-2952(00)00439-1 [pii]
AID - 10.1016/s0006-2952(00)00439-1 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2000 Nov 1;60(9):1285-96. doi: 10.1016/s0006-2952(00)00439-1.