Disease relevance of Eicosatetraynoic acid

• In support of this hypothesis, we report that the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA, 5 mumol/L) and eicosatetraynoic acid (7 mumol/L) added just before and during preconditioning blocked the protective effects of preconditioning on recovery of function during reflow after 30 minutes of global ischemia [1].
• When human PC-3 cells derived from a metastatic prostatic adenocarcinoma were incubated for 15 min to 4 h with the in vitro inhibitor of eicosanoid biosynthesis, eicosatetraynoic acid (ETYA) at 10-80 microM, DNA synthesis was suppressed [2].
• In ETYA-treated and cowpox virus-infected cells, early and late gene expression were near normal levels, whereas the assembly of virus-specific membranes was severely reduced [3].
• Further studies in vitro showed that the drugs ETYA and BW755c were effective in inhibiting the replication of two additional orthopoxviruses, ectromelia and vaccinia viruses, but not human parainfluenza virus-3 [3].
• In cultures of dorsal root ganglion neurons, inhibitors of arachidonate release (mepacrine, 4-bromphenacyl bromide) or its subsequent metabolism by lipoxygenases (nordihydroquaiaretic acid, eicosatetraynoic acid) also prevent the early morphological events of nerve fiber growth [4].

High impact information on Eicosatetraynoic acid

• C/EBP beta can induce PPAR gamma mRNA in the absence of ETYA; however, expression of aP2 mRNA and maximum fat deposition is dependent on the PPAR activator [5].
• Furthermore, several other peroxisome proliferators, such as the fibrate, Wy-14643, and the fatty acid, eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription [6].
• AGEPC-induced aggregation is attenuated by two inhibitors of arachidonate lipoxygenation, eicosatetraynoic acid and nordihydroguaiaretic acid, and to a lesser extent by the cyclooxygenase inhibitor, indomethacin [7].
• Suppression of LOX diene conjugation by *NO was also found, although the lipid product profile was unchanged. *NO consumption by porcine monocytes was inhibited by the LOX inhibitor, eicosatetraynoic acid [8].
• Only the amide derivatives of ETYA and meclofenamic acid inhibit COX-2; the esters are either inactive or nonselective [9].

Chemical compound and disease context of Eicosatetraynoic acid

• Indomethacin or eicosatetraynoic acid (EYA) increased tone and inhibited the relaxation produced by anoxia or hypoxia [10].
• The arrhythmias induced by the arrhythmogenic prostaglandins and thromboxane A2 could be suppressed by the nonmetabolizable AA analog eicosatetraynoic acid (ETYA) or free AA and EPA, indicating a distinction in the effect on cardiac arrhythmia between the precursor fatty acids (AA & EPA) themselves and their metabolites [11].
• Transient transfection experiments with HepG2 hepatoma cells showed that ETYA and clofibric acid decreased the transcriptional activity of the 7 kb regulatory region of the rat AFP gene [12].

Biological context of Eicosatetraynoic acid

• Two other lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, were less potent (IC50 0.09 and 0.15 mM, respectively) [13].
• By mutagenesis analyses we identify amino acid residues in the ligand binding domains of Xenopus, mouse and human PPAR alpha, that confer preferential responsiveness to ETYA and Wy 14,643 [14].
• It is concluded that the inhibitors of eicosanoid biosynthesis, NDGA and (to a lesser extent) ETYA, reduce in vitro cell proliferation in two glioma lines from both the rat and human [15].
• Lipoxygenase inhibitors nordihydroguaiaretic acid, eicosatetraynoic acid and plamitoyl ascorbate prevented H2O2-induced DNA fragmentation and ultraweak luminescence, only when added together with H2O2, but not when added 8 h afterwards [16].
• However, eicosatetraynoic acid (100 microM), a cyclooxygenase and lipoxygenase inhibitor, added with MPG reduced ischemia/reperfusion-induced lipid peroxidation by 80%, which was significantly greater than the protective effect exhibited by MPG alone [17].

Anatomical context of Eicosatetraynoic acid

• Treatment of neutrophils with pancreatic PLA2 also induced an increase in the activity of the cytosolic PLA2; this response was inhibited by both eicosatetraynoic acid or LY 255283 [18].
• In addition we show that eicosatetraynoic acid, an irreversible inhibitor of lipoxygenase used to mimic the effect of substrate binding, does not alter the overall conformation of LOX-1 nor its ability to bind to membranes [19].
• The addition of PGs to BALB/c 3T3 cells also overcame indomethacin- and eicosatetraynoic acid-inhibited responses to EGF [20].
• Under the same conditions, several LO inhibitors (eicosatetraynoic acid (ETYA), piriprost, and A-64077) almost completely inhibited the modification of LDL by macrophages [21].
• Similarly, 5,8,11,14 eicosatetraynoic acid (ETYA), another inhibitor of the arachidonic acid pathway, blocked the induction of transcripts for TNF-alpha, and both IL-1 genes in phorbol ester-stimulated HL 60 cells [22].

Associations of Eicosatetraynoic acid with other chemical compounds

• Addition of indomethacin (cyclooxygenase inhibitor), A63162 (5'-lipoxygenase inhibitor), or eicosatetraynoic acid (cyclooxygenase/lipoxygenase inhibitor) to the incubations caused little change in the production of [3H]PAF in the differentiated cells supplemented with 20:4 for 24 h [23].
• Inhibition of 5-lipoxygenase with either eicosatetraynoic acid or zileuton prevented the AA-induced increase in PLA2 activity but had no effect on the response induced by LTB4 [18].
• Arachidonic acid analogues 5,8,11 eicosatriynoic acid and 5,8,11,15 eicosatetraynoic acid inhibit the release of both mediators in the range 10(-6) to 10(-4) mol/L with almost total (80% to 100%) inhibition of release at 10(4) mol/L [24].
• 4 SRS-A release induced by A23187 in vitro is inhibited by dexamethasone, indomethacin 1-P-3-P, eicosatetraynoic acid (ETA) and 15-hydroperoxy arachidonic acid [25].
• Effects of eicosatetraynoic acid (ETYA) on cultured pig thyroid cells. Relationships between the inhibition of the phosphatidate-phosphatidyl inositol cycle, the iodination and the cyclic AMP responsiveness to thyrotropin [26].

Gene context of Eicosatetraynoic acid

• The activity of enzymes of both pathways were inhibited by 5,8,11,13-eicosatetraynoic acid (ETYA) and nor-dihydroguaretic acid (NDGA), known inhibitors of the lipoxygenase and cyclooxygenase pathways [27].
• This stimulatory effect on PGHS-2 synthesis was prevented by an AA utilization inhibitor, eicosatetraynoic acid [28].
• In fact, ETYA prevented the suppression of hepatic fatty acid synthase expression that characteristically results from feeding corn oil [29].
• Moreover, 5,8,11-eicosatriynoic acid (ETI) which inhibits 5- and 12-LO, and 5, 8, 11, 14-eicosatetraynoic acid (ETYA) which inhibits all known LOs did not affect B-lymphocyte proliferation [30].
• Relaxation due to these agents was also inhibited by exposure to nordihydroguaiaretic acid, a lipoxygenase inhibitor, and eicosatetraynoic acid, a lipoxygenase and cyclooxygenase inhibitor [31].

Analytical, diagnostic and therapeutic context of Eicosatetraynoic acid

• Eicosatetraynoic acid and eicosatriynoic acid behave similarly in the extraction system chosen, yet can be easily resolved by gas-liquid chromatography [32].

References