5-OxoETE
(Synonyms: 5-KETE) 目录号 : GC40380A polyunsaturated keto acid?that stimulates neutrophil migration
Cas No.:106154-18-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
5-OxoETE is a polyunsaturated keto acid formed by the oxidation of 5-HETE in human neutrophils by a specific dehydrogenase.[1] It stimulates cytosolic calcium levels in neutrophils with an EC50 value of 2 nM.[2] 5-OxoETE selectively stimulates the migration and degranulation of eosinophils and activates the MAPK pathway in stimulated neutrophils via a specific G protein-coupled receptor.[3],[4],[5],[6]
Reference:
[1]. Powell, W.S., Gravelle, F., and Gravel, S. Metabolism of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid and other 5(S)-hydroxyeicosanoids by a specific dehydrogenase in human polymorphonuclear leukocytes. J. Biol. Chem. 267(27), 19233-19241 (1992).
[2]. Powell, W.S., Zhang, Y., and Gravel, S. Effects of phorbol myristate acetate on the synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid by human polymorphonuclear leukocytes. Biochemistry 33(13), 3927-3933 (1994).
[3]. O'Flaherty, J.T., Kuroki, M., Nixon, A.B., et al. 5-Oxo-eicosanoids and hematopoietic cytokines cooperate in stimulating neutrophil function and the mitogen-activated protein kinase pathway. J. Biol. Chem. 271(30), 17821-17828 (1996).
[4]. O'Flaherty, J.T., Kuroki, M., Nixon, A.B., et al. 5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes. J. Immunol. 157(1), 336-342 (1996).
[5]. Hosoi, T., Koguchi, Y., Sugikawa, E., et al. Identification of a novel human eicosanoid receptor coupled to Gi/o. J. Biol. Chem. 277 (35), 31459-31465 (2002).
[6]. Jones, C.E., Holden, S., Tenaillon, L., et al. Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol. Pharmacol. 63(3), 471-477 (2003).
| Cas No. | 106154-18-1 | SDF | |
| 别名 | 5-KETE | ||
| 化学名 | 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid | ||
| Canonical SMILES | CCCCC/C=C\C/C=C\C/C=C\C=C/C(=O)CCCC(=O)O | ||
| 分子式 | C20H30O3 | 分子量 | 318.5 |
| 溶解度 | DMF: Miscible,DMSO: Miscible,Ethanol: Miscible,PBS pH 7.2: 0.8 mg/ml | 储存条件 | Store at -80°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1397 mL | 15.6986 mL | 31.3972 mL |
| 5 mM | 0.6279 mL | 3.1397 mL | 6.2794 mL |
| 10 mM | 0.314 mL | 1.5699 mL | 3.1397 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
5-OxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D
Sci Signal 2018 Dec 18;11(561):eaal2171.PMID:30563864DOI:10.1126/scisignal.aal2171.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-OxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-OxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-OxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+ imaging of dorsal root ganglion (DRG) neurons. We showed that 5-OxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-OxoETE. Together, these data suggest that 5-OxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-OxoETE may play a pivotal role in the abdominal pain associated with IBS-C.
Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea
Antioxidants (Basel) 2021 Aug 3;10(8):1242.PMID:34439490DOI:10.3390/antiox10081242.
Early detection of obstructive sleep apnea (OSA) is needed to reduce cardiovascular sequelae and mortality. Full-night polysomnography has been used for diagnosing OSA, but it is too expensive and inconvenient for patients to handle. Metabolome-wide analyses were performed to find and validate surrogate markers for OSA. We further investigated the mechanism underlying hypoxic induction of the markers in human cells and mice. Arachidonic acid derivatives 5-HETE and 5-OxoETE were detected in urine samples. The levels (mean ± SD, ng per mg creatinine) of 5-HETE and 5-OxoETE were 56.4 ± 26.2 and 46.9 ± 18.4 in OSA patients, respectively, which were significantly higher than those in controls (22.5 ± 4.6 and 18.7 ± 3.6). Both levels correlated with the apnea-hypopnea index and the lowest oxygen saturation on polysomnography. After the treatment with the continuous positive airway pressure, the metabolite levels were significantly reduced compared with those before the treatment. In human mononuclear cells subjected to intermittent hypoxia, 5-HETE and 5-OxoETE productions were induced by hypoxia-inducible factor 1 and glutathione peroxidase. When mice were exposed to intermittent hypoxia, 5-HETE and 5-OxoETE were excreted more in urine. They were identified and verified as new OSA markers reflecting hypoxic stress. The OSA markers could be used for OSA diagnosis and therapeutic evaluation.
Expression of 5-OxoETE receptor in prostate cancer cells: critical role in survival
Biochem Biophys Res Commun 2006 Jan 6;339(1):93-8.PMID:16289380DOI:10.1016/j.bbrc.2005.10.189.
Previously, we reported that metabolism of arachidonic acid through the 5-lipoxygenase (5-LOX) pathway plays an important role in the survival and growth of human prostate cancer cells. Inhibition of 5-LOX by pharmacological inhibitors triggers apoptosis in prostate cancer cells within hours of treatment, which is prevented by the metabolites of arachidonate 5-lipoxygenase, 5(S)-hydroxyeicosatetraenoic acid (5(S)-HETE), and its dehydrogenated derivative, 5-oxoeicosatetraenoic acid (5-OxoETE). These findings suggested that 5-lipoxygenase metabolites are critical survival factors of prostate cancer cells. However, molecular mechanisms by which 5(S)-HETE and its derivative 5-OxoETE exert their effects on prostate cancer cell survival are yet to be understood. Here, we report that human prostate cancer cells differentially express a G-protein-coupled 5-OxoETE receptor (5-oxoER) in them. Blocking expression of 5-oxoER by short-interfering RNA (siRNA) significantly reduced the viability of prostate cancer cells, suggesting that 5-oxoER is critical for prostate cancer cell survival, and that the 5-LOX metabolite, 5-OxoETE, controls survival of prostate cancer cells through its own G-protein-coupled receptor, 5-oxoER.
5-Oxo-eicosanoids and hematopoietic cytokines cooperate in stimulating neutrophil function and the mitogen-activated protein kinase pathway
J Biol Chem 1996 Jul 26;271(30):17821-8.PMID:8663432DOI:10.1074/jbc.271.30.17821.
The newly defined eicosatetraenoates (ETEs), 5-OxoETE and 5-oxo-15(OH)-ETE, share structural motifs, synthetic origins, and bioactions with leukotriene B4 (LTB4). All three eicosanoids stimulate Ca2+ transients and chemotaxis in human neutrophils (PMN). However, unlike LTB4, 5-OxoETE and 5-oxo-15(OH)-ETE alone cause little degranulation and no superoxide anion production. However, we show herein that, in PMN pretreated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM-CSF or G-CSF), the oxoETEs become potent activators of the last responses. The oxoETEs also induce translocation of secretory vesicles from the cytosol to the plasmalemma, an effect not requiring cytokine priming. To study the mechanism of PMN activation in response to the eicosanoids, we examined the activation of mitogen-activated protein kinase (MAPK) and cytosolic phospholipase A2 (cPLA2). PMN expressed three proteins (40, 42, and 44 kDa) that reacted with anti-MAPK antibodies. The oxoETEs, LTB4, GM-CSF, and G-CSF all stimulated PMN to activate the MAPKs and cPLA2, as defined by shifts in these proteins' electrophoretic mobility and tyrosine phosphorylation of the MAPKs. However, the speed and duration of the MAPK response varied markedly depending on the stimulus. 5-OxoETE caused a very rapid and transient activation of MAPK. In contrast, the response to the cytokines was rather slow and persistent. PMN pretreated with GM-CSF demonstrated a dramatic increase in the extent of MAPK tyrosine phosphorylation and electrophoretic mobility shift in response to 5-OxoETE. Similarly, 5-OxoETE induced PMN to release some preincorporated [14C]arachidonic acid, while GM-CSF greatly enhanced the extent of this release. Thus, the synergism exhibited by these agents is prominent at the level of MAPK stimulation and phospholipid deacylation. Pertussis toxin, but not Ca2+ depletion, inhibited MAPK responses to 5-OxoETE and LTB4, indicating that responses to both agents are coupled through G proteins but not dependent upon Ca2+ transients. 15-OxoETE and 15(OH)-ETE were inactive while 5-oxo-15(OH)-ETE and 5(OH)-ETE had 3- and 10-fold less potency than 5-OxoETE, indicating a rather strict structural specificity for the 5-keto group. LY 255283, a LTB4 antagonist, blocked the responses to LTB4 but not to 5-OxoETE. Therefore, the oxoETEs do not appear to operate through the LTB4 receptor. In summary, the oxoETEs are potent activators of PMN that share some but not all activities with LTB4. The response to the oxoETEs is greatly enhanced by pretreatment with cytokines, indicating that combinations of these mediators may be very important in the pathogenesis of inflammation.
Receptors for the 5-oxo class of eicosanoids in neutrophils
J Biol Chem 1998 Dec 4;273(49):32535-41.PMID:9829988DOI:10.1074/jbc.273.49.32535.
5-Hydroxy- and 5-oxo-eicosatetraenoate (5-HETE and 5-OxoETE) activate polymorphonuclear neutrophils (PMNs) through a common, receptor-like recognition system. To define this system, we examined the interaction of these eicosanoids with human PMNs. PMNs esterified 5-[3H]HETE to glycerolipids at 37 and 4 degreesC. At 37 but not 4 degreesC, the cells also hydroxylated the label to 5, 20-[3H]diHETE. The acyl:CoA synthetase blocker, triacsin C, inhibited esterification but also led to an increase in the hydroxylation of the label. PMNs processed 5-[3H]oxoETE through the same pathways but only or principally after reducing it to 5-[3H]HETE (37 or 4 degreesC). In the presence of these varying metabolic reactions, PMNs (37 or 4 degreesC; +/- triacsin C) could not be shown to receptor bind either radiolabel. Plasma membranes isolated from PMNs esterified but unlike whole cells did not reduce or hydroxylate 5-[3H]oxoETE. Triacsin C blocked esterification, thereby rendering the membranes unable to metabolize this radiolabel. Indeed, triacsin C-treated membranes bound (Kd = 3.8 nM) 5-[3H]oxoETE specifically and reversibly to 86 pmol of sites per 25 micrograms of membrane protein. 5-OxoETE, 5-HETE, and 5,15-diHETE displaced this binding at concentrations correlating with their potency in eliciting PMN Ca2+ transients. GTP and GTPgammaS, but not ATP or ATPgammaS, also reduced 5-[3H]oxoETE binding, whereas 15-HETE, leukotriene B4, platelet-activating factor, IL-8, C5a, and N-formyl-Met-Leu-Phe lacked this effect. We conclude that PMNs and their plasma membranes use an acyl:CoA synthetase-dependent route to esterify 5-HETE and 5-OxoETE into lipids. Blockade of the synthetase uncovers cryptic plasmalemma sites that bind 5-OxoETE with exquisite specificity. These sites apparently mediate responses to the 5-oxo class of eicosanoids and are likely members of the serpentine superfamily of G protein-linked receptors.