Arachidonic acid induces endothelin-1 gene expression in vascular endothelial cells

J Cell Biochem. 1999 Dec 15;75(4):724-33.

Abstract

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide synthesized and secreted by vascular endothelial cells. Regulation of ET-1 production occurs at the level of gene transcription. We previously demonstrated a role for arachidonic acid as an intracellular mediator in the regulation of gene expression. This study investigated the role of arachidonic acid in induction of ET-1 production in endothelial cells. Challenge of bovine aortic endothelial cells (BAECs) with arachidonic acid induced a dose- and time-dependent increase in the amount of immunoreactive ET-1 in the supernatant. The maximum effect was observed at concentrations of 20 microM. Release of ET-1 by arachidonic acid was preceded by induction of ET-1 gene expression. Arachidonic acid increased ET-1 gene expression by increasing transcription of the ET-1 gene. The effect of arachidonic acid was mimicked by other polyunsaturated fatty acids, whereas saturated fatty acids had no effect. Moreover, inhibitors of the lipoxygenase pathway blocked arachidonic acid-induced release of ET-1. These results suggest that arachidonic acid stimulated the production of ET-1 in BAECs by inducing ET-1 gene transcription. Arachidonic acid-induced production of ET-1 is dependent on lipoxygenase products of arachidonate metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / antagonists & inhibitors
  • Arachidonic Acid / pharmacology*
  • Cattle
  • Cell Line
  • Culture Media, Conditioned / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelin-1 / biosynthesis
  • Endothelin-1 / genetics*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Fatty Acids / pharmacology
  • Gene Expression / drug effects*
  • L-Lactate Dehydrogenase / metabolism
  • Lipoxygenase Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Culture Media, Conditioned
  • Cyclooxygenase Inhibitors
  • Endothelin-1
  • Fatty Acids
  • Lipoxygenase Inhibitors
  • RNA, Messenger
  • Arachidonic Acid
  • L-Lactate Dehydrogenase