Detection of a novel cyclooxygenase metabolite produced by human promyelocytic leukemia (HL-60) cells.
Arachidonic acid metabolism via the lipoxygenase pathway was examined in HL-60 cells before and after N,N-dimethylformamide induced differentiation along granulocytic lines. Untreated HL-60 cells produced small amounts of the 5-lipoxygenase products, 5-hydroxy-eicosatetraenoic acid and leukotriene B4 upon stimulation with calcium ionophore A23187. N,N-dimethylformamide treatment, caused a 10 to 20 fold increase in the amount of ionophore A23187-induced 5-lipoxygenase metabolites. An additional, and as yet unidentified arachidonic acid metabolite was routinely observed during reverse-phase high pressure liquid chromatography analyses of lipoxygenase products. Sensitivity to inhibition by less than 10(-7)M indomethacin coupled with other characteristics of its production, strongly suggest the compound is a cyclooxygenase product. The unusual UV absorbance and chromatographic elution pattern, however, suggest that it is not a typical prostaglandin, thromboxane or prostacyclin product.
Agins
A P
AP
Hollmann
A B
AB
Agarwal
K C
KC
Wiemann
M C
MC
D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases