TY - JOUR
T1 - Formation of a novel 20-hydroxylated metabolite of lipoxin A4 by human neutrophil microsomes
AU - Sumimoto, Hideki
AU - Isobe, Ryuichi
AU - Mizukami, Yoichi
AU - Minakami, Shigeki
N1 - Funding Information:
AcknowledgementsT. his work was supportedin part by grantsf rom the Ministry of Education,S ciencea nd Culture,J apan.
PY - 1993/1/11
Y1 - 1993/1/11
N2 - Lipoxin A4 (LXA4) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA4 either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse-phase high-performance liquid chromatography. We have identified the metabolite as 20-hydroxy-LXA4, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The LXA4ω -hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH-cytochrome P-450 reductase, or competitively by leukotriene B4 (LTB4) and LTB5, substrates of LTB4 ω-hydroxylase. These findings indicate that the formation of 20-hydroxy-LXA4 is catalyzed by a neutrophil cytochrome P-450, the LTB4 ω-hydroxylase.
AB - Lipoxin A4 (LXA4) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA4 either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse-phase high-performance liquid chromatography. We have identified the metabolite as 20-hydroxy-LXA4, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The LXA4ω -hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH-cytochrome P-450 reductase, or competitively by leukotriene B4 (LTB4) and LTB5, substrates of LTB4 ω-hydroxylase. These findings indicate that the formation of 20-hydroxy-LXA4 is catalyzed by a neutrophil cytochrome P-450, the LTB4 ω-hydroxylase.
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U2 - 10.1016/0014-5793(93)81165-V
DO - 10.1016/0014-5793(93)81165-V
M3 - Article
C2 - 8422907
AN - SCOPUS:0027506998
SN - 0014-5793
VL - 315
SP - 205
EP - 210
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -