Upregulation of Endothelin-1 Production by Lysophosphatidic Acid in Rat Aortic Endothelial Cells
Addition of lysophosphatidic acid (LPA) to rat aorta-derived endothelial cells significantly induced preproendothelin-1 (preproET-1) mRNA expression. PreproET-1 mRNA levels reached a plateau within 1 h after the addition of 0.5 μM LPA and declined after 2 h. The induction was superinduced by cycloheximide and was blocked by actinomycin D. Suramin, an LPA receptor antagonist, abolished the induction of preproET-1 mRNA by LPA. Protein kinase C inhibitors, H7 and bisindolylmaleimide, were able to block the induction. Transient transfection experiment revealed that the elevated preproET-1 mRNA was a result of the activation of ET-1 gene activity. Electrophoretic mobility shift assay revealed that LPA stimulated the binding of AP-1. The secreted level of ET-1 was elevated 2.3-fold after 12 h of stimulation with LPA. Our results suggest that the upregulation of preproET-1 by LPA may serve to augment and prolong the vasoconstriction action of LPA.
Chua, Chu Chang; Hamdy, Ronald C.; and Chua, Balvin H.L.. 1998. Upregulation of Endothelin-1 Production by Lysophosphatidic Acid in Rat Aortic Endothelial Cells. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1405(1-3). 29-34. https://doi.org/10.1016/S0167-4889(98)90093-3 PMID: 9784597 ISSN: 0167-4889