PMID- 9890193
OWN - NLM
STAT- MEDLINE
DCOM- 19990310
LR  - 20191102
IS  - 1095-6670 (Print)
IS  - 1095-6670 (Linking)
VI  - 13
IP  - 2
DP  - 1999
TI  - Linoleic acid amplifies polychlorinated biphenyl-mediated dysfunction of 
      endothelial cells.
PG  - 83-91
AB  - Selected dietary lipids may increase the atherogenicity of environmental 
      chemicals, such as polychlorinated biphenyls (PCBs), by cross-amplifying 
      mechanisms leading to dysfunction of the vascular endothelium. To investigate 
      this hypothesis, cultured endothelial cells were treated with 90 microM linoleic 
      acid (18:2n-6), followed by either one of two PCBs, 3,3',4,4'-tetrachlorobiphenyl 
      (PCB 77) or 2,2'4,4',5,5'-hexachlorobiphenyl (PCB 153). These PCBs were selected 
      for their varying binding activities with the aryl hydrocarbon (Ah) receptor and 
      differences in their induction of cytochrome P450. PCB 77 disrupted endothelial 
      barrier function by allowing an increase in albumin transfer across endothelial 
      monolayers. Prior cellular enrichment with 18:2 before PCB treatment further 
      diminished endothelial barrier function, as compared to cells treated only with 
      the PCB. This phenomenon appears to be mediated by increased oxidative stress, 
      which is supported by enhanced 2,7-dichlorofluorescein fluorescence, activation 
      data of the oxidative stress-sensitive nuclear transcription factor-kappaB 
      (NF-kappaB), as well as an observed decrease in vitamin E content in the culture 
      media. Similar to the endothelial permeability data, pre-enrichment of cells with 
      18:2 further increased the PCB-mediated induction of cytochrome P450 1A. In 
      contrast to PCB 77, PCB 153 (or 18:2 plus PCB 153) had little or no effect on 
      endothelial barrier function. Our results suggest that certain unsaturated fatty 
      acids can potentiate PCB-mediated endothelial cell dysfunction and that oxidative 
      stress and activation of the cytochrome P450 1A subfamily may be, in part, 
      responsible for these metabolic events. These findings have implications for 
      understanding the involvement of certain environmental contaminants in diseases 
      that involve dysfunction of the vascular endothelium.
FAU - Hennig, B
AU  - Hennig B
AD  - Department of Nutrition and Food Science, Graduate Center for Toxicology, 
      University of Kentucky, Lexington 40506-0054, USA.
FAU - Slim, R
AU  - Slim R
FAU - Toborek, M
AU  - Toborek M
FAU - Robertson, L W
AU  - Robertson LW
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - 1 P42 ES 07380/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 0 (DNA Primers)
RN  - 0 (NF-kappa B)
RN  - 9KJL21T0QJ (Linoleic Acid)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - DNA Primers
MH  - Endothelium, Vascular/*drug effects/enzymology/metabolism
MH  - Linoleic Acid/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Polychlorinated Biphenyls/*pharmacology
MH  - Swine
EDAT- 1999/01/16 03:13
MHDA- 2000/08/12 11:00
CRDT- 1999/01/16 03:13
PHST- 1999/01/16 03:13 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 1999/01/16 03:13 [entrez]
AID - 10.1002/(SICI)1099-0461(1999)13:2<83::AID-JBT4>3.0.CO;2-7 [pii]
AID - 10.1002/(sici)1099-0461(1999)13:2<83::aid-jbt4>3.0.co;2-7 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 1999;13(2):83-91. doi: 
      10.1002/(sici)1099-0461(1999)13:2<83::aid-jbt4>3.0.co;2-7.