Structural requirements of cyclopentenone prostaglandins to induce endothelial cell apoptosis.
Prostaglandins are a family of structurally related molecules formed by many cells in response to extrinsic stimuli. A member of this family, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), shows unique biological properties including anti-inflammatory, anti-viral, and anti-tumour activity, and has attracted much attention as a high affinity ligand for the peroxisome proliferator-activated receptor gamma. Increasing evidence points to additional effects. We investigated several structurally related prostaglandins in comparison to 15d-PGJ(2) with respect to their apoptosis-inducing capacity in human umbilical endothelial cells (HUVEC). Cell viability was tested with a modified MTT assay and apoptosis was detected by Annexin V staining and cell cycle analysis by flow cytometry. Incubation of confluent HUVECs with 15d-PGJ(2) markedly reduced endothelial cell viability which was due to apoptosis. In contrast, none of the other PGs tested affected cell viability. Interestingly, the cyclopentenone ring alone dose-dependently reduced cell viability and significantly induced apoptosis in HUVECs with as low a concentration as 0.25 microM. In conclusion, we report that the cyclopentenone moiety of cyPGs is an essential component for the apoptosis-inducing properties of 15d-PGJ(2). For 15d-PGJ(2) the position of the cyclopentenone ring in conjunction with the side chains yields a molecule with unique biological properties.
Vosseler
Claudia A
CA
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Munich, Germany. cvossele@klp.med.uni-muenchen.de
Erl
Wolfgang
W
Weber
Peter C
PC
D017209:Apoptosis; D002460:Cell Line; D003517:Cyclopentanes / Q000737:chemistry* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D015394:Molecular Structure; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011453:Prostaglandins / Q000737:chemistry* / Q000494:pharmacology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D011453:Prostaglandins; C013905:cyclopentenone; D015230:Prostaglandin D2