Inhibition of prostaglandin synthesis after metabolism of menadione by cultured porcine endothelial cells

The Journal of Clinical Investigation
A BarchowskyA R Whorton

Abstract

We have examined the effects of menadione on porcine aortic endothelial cell prostaglandin synthesis. Addition of 1-20 microM menadione caused a dose- and time-dependent inhibition of stimulated prostaglandin synthesis with an IC50 of 5 microM at 15 min. Concentrations greater than 100 microM menadione were necessary to increase 51Cr release from prelabeled cells. Recovery of enzyme inactivated by menadione required a 6-h incubation in 1% serum. In a microsomal preparation, menadione was shown to have no direct effect on conversion of arachidonic acid to prostaglandins. In intact cells menadione caused only a 40% inhibition of the conversion of PGH2 to prostacyclin. Enzymes involved in the incorporation and the release of arachidonic acid were not affected by menadione (20 microM, 15 min). Menadione undergoes oxidation/reduction reactions in intact cells leading to partial reduction of oxygen-forming, reactive oxygen species. In our cells menadione was found to increase KCN-resistant oxygen consumption. Further, an increased accumulation of H2O2 was observed with a time course consistent with menadione-induced inhibition of prostaglandin synthesis. We conclude that menadione at sublethal doses caused inhibition of prostaglandin...Continue Reading

References

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Citations

Jan 1, 1991·Life Sciences·C C BenzA Barchowsky
Jun 1, 1994·Free Radical Biology & Medicine·A BarchowskyK P Chepenik
Jan 1, 1996·Free Radical Biology & Medicine·A BarchowskyK E Wetterhahn
Nov 19, 2003·Prostaglandins, Leukotrienes, and Essential Fatty Acids·J XuG Y Sun
Aug 7, 2003·Toxicology and Applied Pharmacology·Kimberley A O'HaraAaron Barchowsky
Aug 1, 1992·The American Journal of the Medical Sciences·E R Block
Aug 1, 1991·Toxicology and Applied Pharmacology·J F Ghersi-EgeaG Siest
Aug 28, 2014·Endocrine·Giovanni LombardiGiuseppe Banfi
Feb 1, 1992·American Journal of Respiratory Cell and Molecular Biology·V L KinnulaJ D Crapo
Sep 2, 1998·The American Journal of Physiology·R MotterliniM Intaglietta

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