Disease relevance of 5,8,11,14-eicosatetraynoic acid

• The combined cyclooxygenase/lipoxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid (ETYA) also completely block the effect of BK on Isc but the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712 has no effect [1].
• Reduced growth rate of transplantable mammary adenocarcinoma in C3H mice fed eicosa-5,8,11,14-tetraynoic acid [2].
• ETYA had no effect on food intake or weight gain, but it completely prevented 18:2(n-6) from suppressing the hepatic abundance of fatty acid synthase mRNA [3].
• Suppression of rat liver fatty acid synthesis by eicosa-5,8,11,14-tetraynoic acid without a reduction in lipogenic enzymes [4].
• Inhibitors of arachidonic acid metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA), BW755c, and nordihydroguaiaretic acid were found to specifically interfere with the replication of cowpox virus (an orthopoxvirus) both in vivo and in vitro [5].

High impact information on 5,8,11,14-eicosatetraynoic acid

• Exposure of these stimulated cells to a PPAR activator 5,8,11,14-eicosatetraynoic acid (ETYA) results in the accumulation of fat droplets and expression of the adipocyte-enriched genes aP2 and glycerol phosphate dehydrogenase (GPD) [6].
• The neutrophil downregulatory effect on thrombin-stimulated platelets was amplified by lipoxygenase inhibition with 5,8,11,14-eicosatetraynoic acid [7].
• Preincubation of macrophages with the relative lipoxygenase inhibitors nordihydroguaiaretic acid or 5,8,11,14-icosatetraynoic acid inhibited the formation of compound X [8].
• However, the addition of 5,8,11,14-icosatetraynoic acid, an inhibitor of cyclooxygenase and C-12 and C-15 lipoxygenases, completely suppressed the formation of leukotrienes, although this substance is not an inhibitor of the C-5 lipoxygenase in human leukocytes [9].
• When replicating U937 cells were incubated with up to 80 microM concentrations of the in vitro inhibitor of eicosanoid biosynthesis, 5,8,11,14-eicosatetraynoic acid (ETYA), DNA synthesis measured by labeling with [3H]thymidine was inhibited in a concentration-dependent manner [10].

Chemical compound and disease context of 5,8,11,14-eicosatetraynoic acid

• Arachidonic acid metabolism and modulation of in vitro anaphylaxis by 5,8,11,14-eicosatetraynoic acid and 9a,12a-octadecadiynoic acid [11].
• Posttreatment with 5,8,11,14-eicosatetraynoic acid (ETYA), a nonmetabolized competitive inhibitor of arachidonic acid metabolism, or the leukotriene receptor blockers, FPL 55712 and LY 171883, also dramatically reduced the lung weight gain caused by phosgene [12].
• An inhibitor of 5'-lipoxygenase and cyclooxygenase (5,8,11,14-eicosatetraynoic acid), indomethacin, and the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL-55712 all shortened the time to half decay of the contraction, presumably by different mechanisms [13].
• We cultured chronic myelogenous leukemia cells from the peripheral blood of several patients in blast crisis with three inhibitors of lipoxygenases: ETYA, and the more selective A63162 (Abbott) or SC41661A (Searle) [14].

Biological context of 5,8,11,14-eicosatetraynoic acid

• BW 755C (25 microM), a dual cyclooxygenase/lipoxygenase inhibitor, did not modify the vasodilator effect of AA, whereas 5,8,11,14-eicosatetraynoic acid (10 microM), which blocks all pathways of AA metabolism, abolished AA-induced vasodilation, thus suggesting the involvement of nonlipoxygenase AA metabolites [15].
• We have previously shown that AA and its nonmetabolizable analogue, 5,8,11,14-eicosatetraynoic acid (ETYA), inhibit up-regulation of proinflammatory genes in EC [16].
• When cells differentiated by ETYA were cultured in media free of the inhibitor, DNA synthesis reinitiated and the cell number increased; differentiation was phenotypic and not genotypic [17].
• The effects of ETYA on cell division and cell differentiation are closely related but can be dissociated [17].
• On the basis of amino acid sequence comparisons between mammalian 15- and 12-lipoxygenases, three methionine residues in the porcine leukocyte 12-lipoxygenase (M338L, M367V, and M562L) were targeted for mutation to assess their potential role in turnover-dependent inactivation and inhibition by 5,8,11,14-eicosatetraynoic acid (ETYA) [18].

Anatomical context of 5,8,11,14-eicosatetraynoic acid

• Since both basal and stimulated PL metabolism were modified by ETYA and AA, some form of direct regulation of mast cell PL metabolism by AA metabolites seems likely [19].
• Cytotoxic T lymphocyte (CTL)-mediated lysis of target cells was inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA) and other inhibitors of the lipoxygenase pathway at concentrations that inhibited arachidonic acid metabolism in mixed lymphocyte cultures [20].
• A23187-induced eosinophil peroxidase (EPO) release, as measured by guaiacol oxidation, was blocked by eicosa-5,8,11,14-tetraynoic acid (ETYA) (which inhibits both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism) but not by indomethacin (which inhibits only the cyclooxygenase pathway) [21].
• To study further the roles of arachidonate metabolites in the fibroblast response to BK and NP, the cyclooxygenase inhibitor, indomethacin, and the combined lipoxygenase and cyclooxygenase inhibitor, 5,8,11,14-eicosatetraynoic acid (ETYA), were added to fibroblasts prior to BK or NP [22].
• Reticulocyte lipoxygenase was completely inactivated by both 5,8,11-eicosatriynoic and 5,8,11,14-eicosatetraynoic acids in contrast to soybean lipoxygenase-1 which was inactivated only by 5,8,11,14-eicosatetraynoic acid [23].

Associations of 5,8,11,14-eicosatetraynoic acid with other chemical compounds

• Other classes of inhibitors of arachidonate metabolism (i.e., the cyclooxygenase-lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid and phenidone and the phospholipase A2 inhibitor dibromoacetophenone) had inhibitory activity in vitro and in vivo in both stocks of mice [24].
• Evidence for inhibition of leukotriene A4 synthesis by 5,8,11,14-eicosatetraynoic acid in guinea pig polymorphonuclear leukocytes [25].
• The selective lipoxygenases inhibitor 134,7,10,13-eicosatetraynoic acid was more potent than ETYA in inhibition of ESP-induced migration, and the selective cyclooxygenase inhibitor 6,9,12-octadecatriynoic acid did not effect inhibition [26].
• Leukocyte 12-lipoxygenase: expression, purification, and investigation of the role of methionine residues in turnover-dependent inactivation and 5,8,11,14-eicosatetraynoic acid inhibition [18].
• It was found that: (1) dexamethasone, a glucocorticoid agonist and (2) ETI and ETYA, inhibitors of lipoxygenase, had no effect on cell surface TNF-alpha at concentrations that inhibited secreted TNF-alpha [27].

Gene context of 5,8,11,14-eicosatetraynoic acid

• Using 5,8,11,14-eicosatetraynoic acid and inhibitors of AA metabolism, AP-1 and NF-kappaB activation required the lipoxygenase/cytochrome P450 monooxygenase pathways [28].
• However, when assayed in a human liver cell line (HepG2) we noticed that ETYA was a more efficient activator of hPPAR alpha than rPPAR alpha [29].
• Indomethacin and ETYA completely suppressed prostanoids, 11-HETE and 15-HETE formation in resting and IL-1 beta-activated cells [30].
• The calcium influx in response to U46619 (TxA2 analogue) of CD36-deficient platelets was not different from normal platelets in the presence of indomethacin and ETYA [31].
• Incubation of the cell-free preparations with [14C]AA in the presence of ETYA, NDGA (inhibitors of cyclooxygenase and lipoxygenase pathways) as well as with 15-HETE (an inhibitor of lipoxygenase pathway) resulted in decreased formation of [14C] 12-HETE and the [14C]LTB4-like metabolite [32].

Analytical, diagnostic and therapeutic context of 5,8,11,14-eicosatetraynoic acid

• Immunocytochemistry using cGMP antibodies indicated that NHD and ETYA increase cGMP [33].
• Groups of rats were fed a fat-free diet supplemented with 0.5% safflower oil (control) or the control diet containing 0.5% of 5,8,11,14-eicosatetraynoic acid (TYA) [34].
• Intra-arterial infusion of arachidonic acid decreased LES tone, and this was inhibited by intravenous indomethacin (IDM) or intra-arterial 5,8,11,14-eicosatetraynoic acid (ETA) [35].
• Superfusion of hamster cheek pouches with nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (20 microM ETYA), or 100 microM 1-phenyl-3-pyrazolidone (phenidone) decreased (10 microM NDGA) or eliminated (30 microM NDGA, ETYA, or phenidone) the constriction of arterioles induced by elevation of superfusate oxygen tension [36].

References