Linoleic acid amplifies polychlorinated biphenyl-mediated dysfunction of endothelial cells

B. Hennig, R. Slim, M. Toborek, L. W. Robertson

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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 μM 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-κB (NF-κB), 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 PCB153) 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 vas-cular endothelium.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalJournal of Biochemical and Molecular Toxicology
Volume13
Issue number2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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