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- Title
Free-radical–generated F<sub>2</sub> -isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells.
- Authors
Yura, Takafumi; Fukunaga, Megumu; Khan, Rizwan; Nassar, George N.; Badr, Kamal F.; Montero, Angel
- Abstract
Free-radical–generated F2 -isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells. Background. Free-radical–generated F2 -isoprostane stimulates DNA synthesis and endothelin-1 (ET-1) expression on endothelial cells. 8-Iso-prostaglandin F2α (8-iso-PGF2α ) is a member of the recently discovered family of prostanoids, the F2 -isoprostanes, produced in vivo by cyclooxygenase-independent, free-radical-catalyzed lipid peroxidation. The goal of our study is to establish the effect of isoprostane on ET-1 production by endothelial cells, as well to determine the receptors responsible for these effects. Methods. The proliferative effect of isoprostanes was measured as an increase of viable cell number and [3 H]-thymidine uptake. ET-1 gene expression and protein synthesis were determined by Northern blot and radioimmunoassay, respectively. We also determined inositol 1,4,5-trisphosphate synthesis. Thromboxane A2 (TXA2 ) receptor antagonist SQ29,548 was used to establish the role of TXA2 receptor in isoprostane effect, as well as to determine the type of receptors involved in these effects. Results. Our results show that physiological concentrations of 8-iso-PGF2α stimulated cell proliferation, DNA synthesis, and ET-1 mRNA and protein expression in bovine aortic endothelial cells (BAECs). The proliferative effect was partially abolished by treatment with anti-endothelin antibody. 8-Iso-PGF2α also increased inositol 1,4,5-trisphosphate formation in these cells. These effects were partially inhibited by SQ29,548. In competitive binding assays, two binding sites were recognized on BAECs with dissociation constants (Kd) and binding site densities at equilibrium similar to those previously described in smooth muscle cells and likely represent [3 H]-8-iso-PGF2α...
- Subjects
PROSTAGLANDINS; ENDOTHELINS; CELL proliferation
- Publication
Kidney International, 1999, Vol 56, Issue 2, p471
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00596.x