Linoleic acid potentiates TNF-mediated oxidative stress, disruption of calcium homeostasis, and apoptosis of cultured vascular endothelial cells

Michal Toborek, Emmanuelle M. Blanc, Simone Kaiser, Mark P. Mattson, Bernhard Hennig

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72 Scopus citations

Abstract

Diet-derived lipids may influence cytokine-mediated endothelial cell dysfunction, including TNF-induced apoptosis. To test this hypothesis; oxidative stress, intracellular calcium levels, endothelial barrier function, cell viability, and apoptosis were measured in vascular endothelial cells treated with 90 μM linoleic acid (18:2, n-6) and/or 20 ng/mL TNF (100 U/mL). For short-term exposure, endothelial cells were exposed to 18:2 for 6 h or to TNF for 1.5 h. For long-term exposure, endothelial cultures were treated with 18:2 for 24 h and with TNF for 19.5 h. In cells exposed to 18:2 + TNF, pretreatment with 18:2 began 4.5 h before additional exposure to TNF for either 1.5 h (short-term exposure) or 19.5 h (long-term exposure). After treatment, endothelial cultures were washed and incubated with maintenance medium for up to 4 days. Although initial treatment with TNF or 18:2 significantly increased oxidative stress and intracellular calcium levels, only exposure to TNF induced apoptosis in cultured endothelial cells. Furthermore, the combined exposure to 18:2 + TNF potentiated TNF-induced apoptosis. Additional treatments with BAPTA-AM, n-propyl gallate, vitamin E, and with aurintricarboxylic acid partially protected against TNF- or 18:2 + TNF-induced apoptosis. The present study suggests that changes in the cellular lipid environment may markedly influence local TNF-induced events in the vascular endothelium, including endothelial cell apoptosis. Such mechanisms may play a role in the damage and death of vascular endothelial cells in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)2155-2167
Number of pages13
JournalJournal of Lipid Research
Volume38
Issue number10
StatePublished - Oct 1997

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Keywords

  • Antioxidants
  • Apoptosis
  • Atherosclerosis
  • Cytokines
  • Fatty acids
  • Intracellular calcium
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology

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