5-hydroxy-6-8-11-14-eicosatetraenoic-acid has been researched along with 5-15-dihydroxy-6-8-11-13-eicosatetraenoic-acid* in 4 studies
4 other study(ies) available for 5-hydroxy-6-8-11-14-eicosatetraenoic-acid and 5-15-dihydroxy-6-8-11-13-eicosatetraenoic-acid
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Albumin modifies the metabolism of hydroxyeicosatetraenoic acids via 12-lipoxygenase in human platelets.
12-Lipoxygenase and cyclooxygenase 1 are the dominating enzymes that metabolize arachidonic acid in human platelets. In addition to the conversion of arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid, 12-lipoxygenase can also utilize 5(S)-hydroxyeicosatetraenoic acid and 15(S)-hydroxyeicosatetraenoic acid to form 5(S), 12(S)-dihydroxyeicosatetraenoic acid and 14(R), 15(S)-dihydroxyeicosatetraenoic acid, respectively. Furthermore, 15(S)-hydroxyeicosatetraenoic acid works as an inhibitor for 12-lipoxygenase. In the present paper we have studied the influence of albumin on the in vitro metabolism of 5 - and 15 -hydroxyeicosatetraenoic acids, and 5,15 -dihydroxyeicosatetraenoic acid by the platelet 12-lipoxygenase. The presence of albumin reduced the formation of 5(S),12(S)- dihydroxyeicosatetraenoic acid from 5(S)-hydroxyeicosatetraenoic acid, however, it had no effect on the 12(S)-hydroxyeicosatetraenoic acid production from endogenous arachidonic acid. In contrast, when 15(S)-hydroxyeicosatetraenoic acid was incubated with activated platelets, the formation of 14(R), 15(S)- dihydroxyeicosatetraenoic acid was stimulated by the presence of albumin. Furthermore, albumin reduced the inhibitory action 15(S)-hydroxyeicosatetraenoic acid had on 12(S)-hydroxyeicosatetraenoic acid formation from endogenous arachidonic acid. However, addition of exogenous arachidonic acid (20 microm) to the incubations inverted the effects of albumin on the conversion of 15(S)-hydroxyeicosatetraenoic acid to 14(R),15(S)- dihydroxyeicosatetraenoic acid and the production of 12(S)-hydroxyeicosatetraenoic acid in these incubations. Based on the Scatchard equation, the estimates of the binding constants to albumin were 1.8 x 10(5) for 15 -HETE, 1.4 x 10(5) for 12-HETE, and 0.9 x 10(5) for 5 -HETE respectively. These results suggest an important role of albumin for the regulation of the availability of substrates for platelet 12-lipoxygenase. Topics: Arachidonate 12-Lipoxygenase; Blood Platelets; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Protein Binding; Serum Albumin; Substrate Specificity | 1999 |
The suppression of 5-lipoxygenation of arachidonic acid in human polymorphonuclear leucocytes by the 15-lipoxygenase product (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid: structure-activity relationship and mechanism of action.
(15S)-Hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (15-HETE) suppresses in ionophore-A23187-stimulated human polymorphonuclear leucocytes (PMN) the conversion of exogenous arachidonic acid into leukotriene B(4) (LTB4) and (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE). However, contrary to earlier suggestions, 15-HETE is not a genuine 5-lipoxygenase inhibitor under these conditions, but rather suppresses the 5-lipoxygenation of arachidonic acid by switching-over of substrate utilization, as judged from a sizeable formation of labelled (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetr aen oic acid (5,15-diHETE) from 15-[1(-14)C]HETE. Identical results were obtained with human recombinant 5-lipoxygenase. In PMN the formation of 5,15-diHETE is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid, suggesting a crucial role of the hydroperoxide tone of the cell. A comparison of a selection of hydroxypolyenoic fatty acids with respect to their capability of suppressing 5-lipoxygenation of arachidonic acid revealed that 15-mono-hydroxyeicosanoids throughout exhibit the highest inhibitory potencies, whereas the other HETEs, 5,15-diHETE as well as octadecanoids, are modest or poor inhibitors. The R and S enantiomers of 15-HETE do not differ from each other, excluding a receptor-like binding of the 15-hydroxy group. Topics: Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Calcimycin; Fatty Acids, Unsaturated; Humans; Hydroxyeicosatetraenoic Acids; Kinetics; Leukotriene B4; Lipoxygenase Inhibitors; Neutrophils; Recombinant Proteins; Structure-Activity Relationship; Substrate Specificity | 1996 |
Transformations of 5-HETE by activated keratinocyte 15-lipoxygenase and the activation mechanism.
There is convincing evidence that normal cultured human keratinocytes possess a 15-lipoxygenase activity which, however, does not appear to manifest itself without cell membrane damage. When "activated", this enzyme transforms arachidonic acid into 15-hydroxyeicosatetraenoic acid (15-HETE), and linoleic acid into 13-hydroxyoctadecadienoic acid, presumably by peroxidase action on their respective hydroperoxy intermediates. Normal but not membrane-damaged keratinocytes metabolize exogenous 5-HETE, principally by esterifying the eicosanoid intact, primarily in the triacylglycerol fraction. In the present study, membrane-damaged keratinocytes were found to transform 5-HETE to 5,15-diHETE and also to a lipoxin-like group of tetraenes. Similar, if not identical, tetraenes were produced by action of the keratinocyte enzyme on 5(S),15(S)-diHETE, which points to the role of the latter as an intermediate between 5-HETE and the tetraenes. A direction for further study of the mechanism of the "activation" step is presented. Topics: Arachidonate 15-Lipoxygenase; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Enzyme Activation; Esterification; Humans; Hydroxyeicosatetraenoic Acids; Keratinocytes; Kinetics; Linoleic Acids | 1990 |
Differential effects of lipoxygenase products on FMLP and LTB4 evoked neutrophil aggregation.
There is evidence that the endogenous biosynthesis of LTB4 is involved in the aggregation of human neutrophils induced by the chemotactic peptide f-met-leu-phe (FMLP). If LTB4 mediates this aggregatory response, then agents which desensitize neutrophils to LTB4 should inhibit the cellular response to FMLP. Since many lipoxygenase products modulate other neutrophil responses to LTB4 and FMLP, we have investigated the effects of lipoxygenase products on LTB4- and FMLP-initiated aggregation. Prior exposure to low concentrations of LTB4 (0.5-10 nM) inhibited subsequent aggregation to the same agent (50 nM), but it did not influence the response to FMLP (10(-7) M). Relatively high concentrations of 5-HETE (5-50 microM) inhibited aggregation initiated by either stimulus. Although the hydroperoxy derivative 5-HPETE also inhibited the response to LTB4, in the relatively narrow concentration range of 1-4 microM it stimulated FMLP-induced aggregation. This latter effect was confirmed using 12 cell preparations from six separate donors; it (the activity of 5-HPETE) was not mimicked by other 5-lipoxygenase products, including LTB4, nor the dihydroperoxide 8,15-DiHPETE. Our results indicate that neutrophil aggregation in response to LTB4 or FMLP can be selectively potentiated or inhibited. On the basis of these data we conclude that the endogenous synthesis of LTB4 is not directly involved in the neutrophil aggregatory response to FMLP, although the hydroperoxy intermediate 5-HPETE may act to enhance the cellular response. Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Arachidonic Acid; Arachidonic Acids; Cell Aggregation; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lipoxygenase; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils | 1985 |