Cyclooxygenase-derived metabolites of 8,9-epoxyeicosatrienoic acid are potent mitogens for cultured rat glomerular mesangial cells.

Homma T, Zhang JY, Shimizu T, Prakash C, Blair IA, Harris RC
Biochem Biophys Res Commun. 1993 191 (1): 282-8

PMID: 8447831 · DOI:10.1006/bbrc.1993.1214

The mitogenic effects of 11(R)-hydroxy-8,9-epoxyeicosatrienoic acid (EET) enantiomers were investigated in cultured rat glomerular mesangial cells. Both 11(R)-hydroxylated 8(R),9(S)- and 8(S),9(R)-EET at 1 microM stimulated [3H]-thymidine incorporation to 300% and 280%, with 50% maximal effect occurring at 8 x 10(-9) M and 1 x 10(-8) M, respectively. Similar concentration-dependent effects were observed in stimulating induction of the immediate early gene, c-fos. Mitogenic activity of the 11(R)-hydroxylated enantiomers was not affected by prior downregulation of protein kinase C, suggesting involvement of protein kinase C-independent mechanisms. These findings suggest that either trans- or intracellular metabolism of 8,9-EET by cyclooxygenase occurs during inflammatory glomerular diseases and that the resulting metabolites are involved in mesangial cell proliferation.

MeSH Terms (17)

8,11,14-Eicosatrienoic Acid Actins Animals Cell Division Cells, Cultured Dose-Response Relationship, Drug Genes, fos Glomerular Mesangium Kinetics Mitogens Prostaglandin-Endoperoxide Synthases Protein Kinase C Rats RNA, Messenger Stereoisomerism Thymidine Tritium

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