D. Bishop-Bailey, T. Hla
Jun 11, 1999
Citations
10
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459
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Journal
The Journal of Biological Chemistry
Abstract
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a bioactive prostanoid produced by dehydration and isomerization of PGD2, a cyclooxygenase product. It was recently shown to activate the nuclear peroxisome proliferator-activated receptor γ (PPARγ), a critical transcription factor involved in adipocyte and monocyte differentiation. In this report, we show that 15d-PGJ2 is a potent inducer of caspase-mediated endothelial cell apoptosis. PPARα, -δ, and -γ were expressed by endothelial cells, which, when treated with 15d-PGJ2, induced receptor translocation into the nucleus, and an increase in PPAR response element-driven reporter gene expression. Ciglitizone, a selective activator of PPARγ, also induced transcriptional activation and endothelial cell apoptosis. Endothelial apoptosis induced by 15d-PGJ2 was inhibited by treatment of cells with an oligonucleotide decoy to a consensus PPAR response element sequence. Furthermore, overexpression of the PPARγ isotype induced endothelial cell apoptosis, which was further potentiated by 15d-PGJ2 treatment. We conclude that 15d-PGJ2induces endothelial cell apoptosis via a PPAR-dependent pathway. The PPAR pathway may be a therapeutic target for numerous pathologies in which excessive angiogenesis is implicated.