These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Generation of the isoprostane 8-epi-prostaglandin F2alpha in vitro and in vivo via the cyclooxygenases.
    Author: Klein T, Reutter F, Schweer H, Seyberth HW, Nüsing RM.
    Journal: J Pharmacol Exp Ther; 1997 Sep; 282(3):1658-65. PubMed ID: 9316884.
    Abstract:
    F2-isoprostanes are isomers of the prostaglandin PGF2alpha. At least one compound of this group, 8-epi-PGF2alpha, exhibits biological activity, and therefore special interest is focused on the mechanism of isoprostane formation: enzyme catalyzed or radical mediated. We analyzed the formation of isoprostanes in vitro and in vivo. In both systems, purified cyclooxygenase isoenzymes and cell models specific for the cyclooxygenase isoenzymes, 8-epi-PGF2alpha formation could be totally suppressed by cyclooxygenase inhibitors. Indomethacin inhibited concentration-dependent 8-epi-PGF2alpha formation in platelets stimulated with calcium ionophore, arachidonic acid or thrombin. Nordihydroguaiaretic acid, an antioxidant, blocked isoprostane formation with a similar IC50 value as thromboxane B2 synthesis, pointing toward cyclooxygenase as the primary target of inhibition. Based on the turnover number, cyclooxygenase-2 formed higher levels of 8-epi-PGF2alpha than cyclooxygenase-1. Endogenous 8-epi-PGF2alpha production in rat mesangial cells correlated well with the mRNA and protein expression of cyclooxygenase-2 during interleukin-1 induction. However, in contrast to human platelets, which produced different forms of isoprostanes, rat mesangial cells appeared to form only 8-epi-PGF2alpha. Further, this indicates that mesangial cells may represent a cellular origin for renal 8-epi-PGF2alpha formation. Next, we analyzed the formation of isoprostanes in humans. A direct correlation was observed between indomethacin treatment and the decrease in 8-epi-PGF2alpha and isoprostane levels, but compared with other prostanoids the inhibition was less pronounced. In summary, based on the in vitro studies, a clear cyclooxygenase-dependent formation of isoprostanes, especially 8-epi-PGF2alpha, was observed. However, in vivo additional formation via cyclooxygenase enzyme-independent mechanisms is likely.
    [Abstract] [Full Text] [Related] [New Search]