Structural biology16(R)-hydroxy-5,8,11,14-eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes
Section snippets
Materials
HETE standards [16(R)-, 16(S)-, 17-, 18-, 19-, and 20-HETE] and 19-HETE-d3 (99+ atom% deuterium) were synthesized as described previously 15, 18. The standards of lipoxygenase-derived HETEs 5, 8, 11, 12, 15 and octadeuterium-labeled arachidonic acid were obtained from Biomol. All solvents used were HPLC grade (Burdick & Jackson), and other reagents were of the highest grade commercially available. BSTFA and pentafluorobenzyl bromide were obtained from the Aldrich Chemical Co., and [1-14
Results
Incubations of arachidonic acid with human PMNL in the absence of a Ca2+ ionophore resulted in the formation of four radiolabeled products (Fig. 1A). The major peak of radioactivity (D) was unmodified arachidonic acid. The material in peak A contained 10–15% of the radioactivity, and it did not show UV absorbance above 205 nm. The material in peaks B and C, combined, accounted for 5–8% of the total radioactivity injected into the HPLC column, and displayed absorbance at 234 nm (Fig. 1B),
Discussion
Biosynthesis of leukotrienes in PMNL requires calcium influx [2]. In the absence of extracellular calcium, stimulation with PAF or fMLP fails to induce arachidonic acid release and LTB4 synthesis. Addition of Ca2+ with either PAF or fMLP to Ca2+-depleted PMNLs results in a Ca2+ influx proportional to the extracellular concentration of Ca2+ and causes a substantial release of arachidonic acid and synthesis of LTB4[3]. Our previous work has shown that in the absence of Ca2+ influx, PMNL
References (35)
- et al.
Transformation of arachidonic acid and homo-γ-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases
J Biol Chem
(1976) - et al.
Leukotriene B4 is a complete secretagogue in human neutrophilsA kinetic analysis
Biochem Biophys Res Commun
(1982) - et al.
Identification and biological activity of novel ω-oxidized metabolites of leukotriene B4 from human leukocytes
FEBS Lett
(1981) - et al.
A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expression of leukotriene B4 ω-hydroxylase
J Biol Chem
(1993) - et al.
Purification and characterization of recombinant human neutrophil leukotriene B4 ω-hydroxylase (cytochrome P450 4F3)
Arch Biochem Biophys
(1998) - et al.
Oxidation of 20-hydroxyleukotriene B4 to 20-carboxyleukotriene B4 by human neutrophil microsomes. Role of aldehyde dehydrogenase and leukotriene B4 ω-hydroxylase (cytochrome P-450LTBω) in leukotriene B4 ω-oxidation
J Biol Chem
(1990) - et al.
Arachidonic acid monooxygenase and lipoxygenase activities in polymorphonuclear leukocytes
Biochem Pharmacol
(1987) - et al.
Conversion of arachidonic acid to two novel products by a cytochrome P450-dependent mixed-function oxidase in polymorphonuclear leukocytes
Biochem Biophys Res Commun
(1984) - et al.
Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids
J Biol Chem
(1990) - et al.
Cloning, sequencing, and cDNA-directed expression of the rat renal CYP4A2Arachidonic acid ω-hydroxylation and 11,12-epoxidation by CYP4A2 protein
Arch Biochem Biophys
(1996)
Formation of 19(S)-, 19(R)- and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1
J Biol Chem
Chiral acetals, Stereocontrolled synthesis of 16-, 17-, and 18-hydroxyeicosatetraenoic acids, cytochrome P-450 arachidonate metabolites
Tetrahedron Lett
Metabolism of 5,6-epoxyeicosatrienoic acid by the human platelet. Formation of novel thromboxane analogs
J Biol Chem
Cytochrome P450-derived renal HETEs, Storage and release
Kidney Int
bis-Allylic hydroxylation of polyunsaturated fatty acids by hepatic monooxygenases and its relation to the enzymatic and nonenzymatic formation of conjugated hydroxy fatty acids
Arch Biochem Biophys
7-HETE, 10-HETE and 13-HETE are major products of NADPH-dependent arachidonic acid metabolism in rat liver microsomesAnalysis of their stereochemistry, and the stereochemistry of their acid-catalyzed rearrangement
Arch Biochem Biophys
Hydroxyeicosatetraenoic acids (HETEs)
Prog Lipid Res
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