Disease relevance of 15S-HpETE

• Although 20:4n-6 and 15-HETE caused a reduction in production of TNF in mononuclear leukocytes stimulated with phytohaemagglutinin, pokeweed mitogen, concanavalin A, and Staphylococcus aureus, 15-HPETE was far more active [1].
• Here we report that HIV gene expression additionally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several other hydroperoxy fatty acids [2].
• Cytotoxicity of arachidonic acid and of its lipoxygenase metabolite 15-hydroperoxyeicosatetraenoic acid on human breast cancer MCF-7 cells in culture [3].

High impact information on 15S-HpETE

• These fatty acids depressed the expression of TNF mRNA in Mono Mac 6 cells stimulated with LPS; 15-HPETE was fivefold more active than 20:4n-6 and 15-HETE [1].
• Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes [4].
• Incubation of the 15-HETE precursor 15-HPETE with endothelial cells resulted in the formation of four distinct ultraviolet light-absorbing peaks [5].
• Leukocyte preparations convert the hydroperoxy icosatetraenoic acids 5(S)-HPETE and 15(S)-HPETE to the unstable leukotriene epoxides LTA4 and 14,15-LTA4 [6].
• TNF-alpha-induced increased expression of ICAM-1, E-selectin, and VCAM-1 mRNA was significantly depressed by 15-HPETE [7].

Biological context of 15S-HpETE

• A modeled structure of the reduced EcTpx in complex with 15-hydroperoxyeicosatetraenoic acid suggests that the size and shape of the binding site are particularly suited for long fatty acid hydroperoxides consistent with its greater reactivity [8].
• In addition, it was shown that all of the lipoxin isomers formed by the incubation of 15-hydroperoxyeicosatetraenoic acid with human leukocytes were also formed by nonenzymatic hydrolysis of this tetraene epoxide [9].
• Novel role of lipoxygenases in the inflammatory response: promotion of TNF mRNA decay by 15-hydroperoxyeicosatetraenoic acid in a monocytic cell line [10].
• Treatment of HUVEC with a phosphatase inhibitor, calyculin A, augmented both the phosphorylation of PECAM-1 and transmigration of monocyte-like HL-60 cells induced by 15(S)-HPETE [11].
• BACKGROUND: Eicosanoids such as leukotrienes, prostaglandins, lipoxins, and 15-hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchoconstriction, increased microvascular permeability, mucus secretion, and polymorph chemotaxis [12].

Anatomical context of 15S-HpETE

• The data show that human umbilical vein endothelial cells, pretreated with these fatty acids, have a reduced ability to be stimulated by tumor necrosis factor-alpha (TNF-alpha) for enhanced neutrophil and monocyte adhesion; the order of inhibitory activity being 15-HPETE > 15-HETE > 20:4 (n-6) [7].
• Thus, LTB4 and 15 HPETE stimulate both the function and the proliferation of the cytotoxic-suppressor T cell subset [13].
• Microsomes derived from rabbit aortas also synthesized 11,12,15- and 11,14,15-THETAs from 15-HPETE, and pretreatment with the cyctochrome P450 inhibitor, miconazole, blocked the formation of these products [14].
• Induction of suppressor cells from peripheral blood T cells by 15-hydroperoxyeicosatetraenoic acid (15-HPETE) [15].
• Leukotriene formation by a purified reticulocyte lipoxygenase enzyme. Conversion of arachidonic acid and 15-hydroperoxyeicosatetraenoic acid to 14, 15-leukotriene A4 [16].

Associations of 15S-HpETE with other chemical compounds

• To a smaller extent, selenodiglutathione or human thioredoxin also potentiated the reduction of 15-HPETE by HP-TR [17].
• Reaction of manganese-reconstituted prostaglandin endoperoxide synthase (Mn-PGHS) with 15-hydroperoxyeicosatetraenoic acid (15-HPETE) generates two products in nearly equal amounts: 15-hydroxyeicosatetraenoic acid (15-HETE) and 15-ketoeicosatetraenoic acid (15-KETE) [Kulmacz et al. (1994) Biochemistry 33, 5428-5439] [18].
• Hydroperoxide lyase in rabbit leukocytes: conversion of 15-hydroperoxyeicosatetraenoic acid to 15-keto-pentadeca-5,8,11,13-tetraenoic acid [19].
• The 15-hydroperoxyeicosatetraenoic acid (15-HPETE) has been shown to affect platelet aggregation induced by collagen, arachidonic acid (AA), and PGH2-analogue [20].
• Leukotriene B4 and 15-HPETE only induced the acrosome reaction when present throughout the preincubation period, indicating that they may enhance the capacitation process rather than the acrosome reaction [21].

Gene context of 15S-HpETE

• Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation [22].
• Our results show that 15(S)-HPETE, at physiological concentrations, induced activation of protein kinase C in HUVEC and leads to the phosphorylation of PECAM-1, thus facilitating the migration of monocyte-like HL-60 cells across the endothelial cell monolayer [11].
• Of the lipoxygenase metabolites tested at 10(-6) M only 15-HPETE and 15-HETE induced Prl release [23].
• Thromboxane synthase was irreversibly inactivated by 15-hydroxy-9 alpha, 11 alpha-peroxidoprosta-5,13-dienoic acid during catalysis and by treatment of 15-hydroperoxyeicosatetraenoic acid [24].
• Effects of 15-hydroperoxyeicosatetraenoic acid on human lymphocyte sheep erythrocyte rosette formation and response to concanavalin A associated with HLA system [25].

Analytical, diagnostic and therapeutic context of 15S-HpETE

• Aortic homogenates were incubated in the presence of [U-14C]arachidonic acid, [U-14C]arachidonic acid plus 15-lipoxygenase (soybean lipoxidase), or [U-14C]15-hydroxyeicosatetraenoic acid (15-HPETE) and analyzed by reverse phase high pressure liquid chromatography (RP-HPLC) [14].
• Furthermore, careful application of this HPLC technique led to the isolation of two minor [1-14C]-labelled fractions which according to their spectral and chromatographic characteristics, were identical with 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) [26].
• The endoperoxide, PGH2 reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE [27].

References