Premium
Arachidonic acid induces endothelin‐1 gene expression in vascular endothelial cells
Author(s) -
Rizzo Maria Teresa,
Yu Wenmei
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991215)75:4<724::aid-jcb17>3.0.co;2-p
Subject(s) - arachidonic acid , lipoxygenase , endothelin 1 , gene expression , biology , biochemistry , polyunsaturated fatty acid , chemistry , fatty acid , microbiology and biotechnology , gene , enzyme , receptor
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 μM. 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. J. Cell. Biochem. 75:724–733, 1999. © 1999 Wiley‐Liss, Inc.