Disease relevance of 12-Hete

• Platelet-derived 12-hydroxyeicosatetraenoic acid plays an important role in mediating canine coronary thrombosis by regulating platelet glycoprotein IIb/IIIa activation [1].
• Induction of inflammatory mediator release (serotonin and 12-hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid [2].
• They further suggest that in brain injury, the liberation and accumulation of arachidonic acid in cerebral tissues may lead to the production of 12-hydroxyeicosatetraenoic acid within microvessels [3].
• Incubation of human platelets with the hemolysin-producing Escherichia coli strain K-12 (pANN5211) induced the activation of protein kinase C, aggregation of platelets, calcium influx, low amounts of 12-hydroxyeicosatetraenoic acid (12-HETE), and release of serotonin from dense granules [4].
• 12-hydroxyeicosatetraenoic acid (12-HETE), the main eicosanoid in skin, is assumed to have both pathophysiologic effects in inflammatory skin diseases such as psoriasis and atopic eczema and a physiologic role in the biology of cutaneous reparative processes [5].

High impact information on 12-Hete

• Furthermore, cytokine-induced 12-hydroxyeicosatetraenoic acid (12-HETE) production was absent in 12-LO KO islets but present in C57/BL6 islets [6].
• A single intravenous injection of the antibody resulted in enhanced glomerular synthesis of thromboxane (Tx)B2, leukotriene (LT)B4, and 12-hydroxyeicosatetraenoic acid (HETE), whereas that of PGE2 and PGF2 alpha was either unaltered or impaired [7].
• Studies on the mechanism of omega-hydroxylation of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) by unstimulated neutrophils [8].
• The addition of 12-hydroxyeicosatetraenoic acid to P-12LO-/- platelet-rich plasma rescues the hyperresponsive phenotype resulting in a diminished ADP-induced aggregation profile [9].
• Both fluorescence microscopy and flow cytometric analysis reveal that surface expression and/or activation of this tumor cell receptor is enhanced by a phorbol ester [i.e., 12-O-tetradecanoylphorbol-13-acetate (TPA)] and a lipoxygenase metabolite of arachidonic acid; 12-hydroxyeicosatetraenoic acid (i.e., 12-HETE) [10].

Chemical compound and disease context of 12-Hete

• Purified glycolipid from Pseudomonas aeruginosa induced the generation of significant amounts of 12-hydroxyeicosatetraenoic acid (12-HETE) and serotonin release from human platelets [2].

Biological context of 12-Hete

• In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention [11].
• The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in skin physiology and pathophysiology [12].
• Rainbow trout (Oncorhynchus mykiss) macrophages generated lipoxin (LX) A4, LXA5, leukotriene (LT) B4, LTB5 and 12-hydroxyeicosatetraenoic acid (12-HETE) during the phagocytosis of zymosan and Escherichia coli, but not of the yeast Saccharomyces cerevisiae [13].
• Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition [14].
• The synthesis and release of the proaggregatory cyclooxygenase (CO) and lipoxygenase (LO) products, thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively, in platelets were also inhibited by Mg in a dose-dependent manner (IC50 4 to 6 mmol/L) [15].

Anatomical context of 12-Hete

• 12-Hydroxyeicosatetraenoic acid is metabolized by beta-oxidation in mouse peritoneal macrophages. Identification of products and proposed pathway [16].
• The mitogenic effect of 15- and 12-hydroxyeicosatetraenoic acid on endothelial cells may be mediated via diacylglycerol kinase inhibition [17].
• Rabbit, chicken, rat, and dog erythrocytes (10(9) cells/ml) synthesized immunologically active 12-hydroxyeicosatetraenoic acid (12-HETE) when stimulated by the Ca2+ ionophore, A-23187 [18].
• Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid [19].
• To determine the possible role that leukotrienes (LTs) may play in the regulation of cerebral blood flow, the responses of cerebral arterioles to LTs and 12-hydroxyeicosatetraenoic acid (12-HETE) were studied in vivo in rabbits equipped with a cranial window for direct observation of the microcirculation [20].

Associations of 12-Hete with other chemical compounds

• As reported by others, exogenous AA was metabolized to large amounts of cyclooxygenase products, 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid, but far lesser amounts of all 5-lipoxygenase products [21].
• In contrast, 10(-9) M 12-hydroperoxyeicosatetraenoic acid and 10(-8) M 12-hydroxyeicosatetraenoic acid were potent inhibitors of renin secretion [22].
• Leukotriene B4 and 12-hydroxyeicosatetraenoic acid stimulate epidermal proliferation in vivo in the guinea pig [23].
• RESULTS: Under resting conditions, RMC expressed COX-1, COX-2 and 12/15-lipoxygenase and mainly generated prostaglandin (PG)E2, thromboxane (TX)B2, 12-hydroxyeicosatetraenoic acid (12-HETE) and 8-epi-PGF2alpha [24].
• Effect of cholesterol enrichment on 12-hydroxyeicosatetraenoic acid metabolism by mouse peritoneal macrophages [25].

Gene context of 12-Hete

• Evidence that 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid activates p21-activated kinase [26].
• We observe tyrosine phosphorylation of Pyk2, p38, and ERK1/2 but no measurable increase in free AA, 12-hydroxyeicosatetraenoic acid, or thromboxane A2 [27].
• Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids [28].
• We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2), and 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE when cultured in the presence of 2.7 microM (0.75 micrograms/ml) LA; 5-HETE secretion was unchanged [29].
• Additionally, an inhibitory effect (IC50 9.8 +/- 2.0 microM) on the production of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (HHT) was demonstrated, whereas the production and/or releasing of 12-hydroxyeicosatetraenoic acid (12-HETE) was not attenuated by the azole [30].

Analytical, diagnostic and therapeutic context of 12-Hete

• AII stimulated the formation of the 12-LO product 12-hydroxyeicosatetraenoic acid (12-HETE) as measured by ultraviolet detection and HPLC in AA loaded cells and by a specific RIA in unlabeled cells (501 +/- 50 to 990 +/- 10 pg/10(5) cells, P less than 0.02) [31].
• In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography [32].
• Analysis by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives of the metabolite, indicate that the compound is 12-hydroxyeicosatetraenoic acid [3].
• LOX products from all fractions comigrated in thin layer chromatography as 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE [33].
• Medium insulin concentrations were measured by radioimmunoassay, and islet production of the 12-lipoxygenase metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured by enzyme immunoassay [34].

References