The action of erythropoietin is mediated by lipoxygenase metabolites in murine fetal liver cells.
Erythroid progenitor cells synthesize 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) when stimulated by erythropoietin (Ep). Maximal stimulation of 12-HETE production occurred at one hour, whereas 15-HETE activity remained constant in response to Ep for 24 hours. Lipoxygenase-selective inhibitors of arachidonic acid metabolism blocked HETE production and Ep-stimulated growth and differentiation of erythroid progenitor cell-derived colonies (CFU-E). On the other hand, specific inhibitors of cyclooxygenase (aspirin and meclofenamate) did not significantly inhibit Ep-induced erythroid colony formation. It is hypothesized that the stimulation of HETE production from arachidonic acid (AA) is an essential step in the mechanism of action of Ep.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D009637:Masoprocol / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D010716:Phosphatidylinositols / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D010716:Phosphatidylinositols; D011720:Pyrazoles; D004921:Erythropoietin; D002083:Butylated Hydroxyanisole; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009637:Masoprocol; C015429:phenidone; D001241:Aspirin