15-OxoETE
(Synonyms: 15KETE) 目录号 : GC40376
An oxylipin produced by oxidation of the 15-hydroxyl of 15-HETE
Cas No.:81416-72-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
15-OxoETE is produced by oxidation of the 15-hydroxyl of 15-HETE. Whether this is a major pathway of 15-HETE metabolism is yet to be clearly established.
| Cas No. | 81416-72-0 | SDF | |
| 别名 | 15KETE | ||
| Canonical SMILES | CCCCCC(=O)/C=C\C=C\C/C=C\C/C=C\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 -20°C |
| 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。
15-Oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways
Chem Biol Interact 2015 Jun 5;234:144-53.PMID:25450232DOI:10.1016/j.cbi.2014.10.029.
Bioactive lipids govern cellular homeostasis and pathogenic inflammatory processes. Current dogma holds that bioactive lipids, such as prostaglandins and lipoxins, are inactivated by 15-hydroxyprostaglandin dehydrogenase (15PGDH). In contrast, the present results reveal that catabolic "inactivation" of hydroxylated polyunsaturated fatty acids (PUFAs) yields electrophilic α,β-unsaturated ketone derivatives. These endogenously produced species are chemically reactive signaling mediators that induce tissue protective events. Electrophilic fatty acids diversify the proteome through post-translational alkylation of nucleophilic cysteines in key transcriptional regulatory proteins and enzymes that govern cellular metabolic and inflammatory homeostasis. 15PGDH regulates these processes as it is responsible for the formation of numerous electrophilic fatty acids including the arachidonic acid metabolite, 15-oxoeicosatetraenoic acid (15-OxoETE). Herein, the role of 15-OxoETE in regulating signaling responses is reported. In cell cultures, 15-OxoETE activates Nrf2-regulated antioxidant responses (AR) and inhibits NF-κB-mediated pro-inflammatory responses via IKKβ inhibition. Inhibition of glutathione S-transferases using ethacrynic acid incrementally increased the signaling capacity of 15-OxoETE by decreasing 15-oxoETE-GSH adduct formation. This work demonstrates that 15PGDH plays a role in the regulation of cell and tissue homeostasis via the production of electrophilic fatty acid signaling mediators.
Primary saturation of α, β-unsaturated carbonyl containing fatty acids does not abolish electrophilicity
Chem Biol Interact 2021 Dec 1;350:109689.PMID:34634267DOI:10.1016/j.cbi.2021.109689.
Metabolism of polyunsaturated fatty acids results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, α,β-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETE) and mono-saturated metabolites of 15-OxoETE and docosahexaenoic acid-derived 17-oxodocosahexaenoinc acid (17-oxoDHA) in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase 1 (PTGR1), known only for its reduction of the α,β-unsaturated double bond, was not responsible for the saturation of oxo-fatty acids at alternative double bonds. Surprisingly, knockdown of PTGR1 expression by shRNA confirmed its participation in the formation of 15-OxoETE and 17-oxoDHA mono-saturated metabolites. Furthermore, overexpression of PTGR1 in A549 cells increased the rate and total amount of oxo-fatty acid saturation. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties.
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.
Underlying antihypertensive mechanism of egg white-derived peptide QIGLF using renal metabolomics analysis
Food Res Int 2022 Jul;157:111457.PMID:35761693DOI:10.1016/j.foodres.2022.111457.
The kidney is an important target organ in the treatment of hypertension, but the effect of peptide QIGLF with antihypertensive activity on kidneys remains unknown. In the work, we aimed to further understand the hypotensive effects of QIGLF in spontaneously hypertensive rats (SHRs) using widely targeted metabolomics technology to investigate the kidney metabolic profiling variations. After four weeks of oral administration, the results showed different renal metabolomics profiles between QIGLF and model groups. Besides, a total of 10 potential biomarkers were identified, that is, 3-hydroxybutanoate, 20-hydroxyeicosatetraenoic acid, 19(S)-hydroxyeicosatetraenoic acid, 15-OxoETE, L-ornithine, malonate, uridine, uridine 5'-monophosphate, argininosuccinic acid, and N-carbamoyl-L-aspartate. These metabolites might exhibit antihypertensive activity of QIGLF by regulating synthesis and degradation of ketone bodies, arachidonic acid metabolism, pyrimidine metabolism, and arginine biosynthesis. These findings suggest that QIGLF might alleviate hypertension by inhibiting renal inflammation, promoting natriuresis, and regulating renal nitric oxide production.
Chemical and biological characterization of oxo-eicosatetraenoic acids
Biochim Biophys Acta 1994 Dec 15;1201(3):505-15.PMID:7803484DOI:10.1016/0304-4165(94)90083-3.
Eicosatetraenoates (ETEs) with 5-oxo residues are known to induce human neutrophil (PMN) Ca2+ transients and chemotaxis. We find that 5-oxoETE, 5-oxo-8-trans-ETE, 5-oxo-15-hydroxy-ETE, 5-hydroxy-ETE, 5-hydroxy-15-oxoETE, 5,15-dioxoETE, and 5,15-dihydroxy-ETE have respective relative potencies of 10, 5, 3, 1, 0.2, 0.1, and 0.02 in: a) causing PMN to mobilize Ca2+, aggregate, and release small amounts of granule enzymes and b) promoting large degranulation and oxidative burst responses in PMN co-challenged with platelet-activating factor, tumor necrosis factor-alpha, or ATP. Contrastingly, 12(R)-hydroxy-ETE, 12(S)-hydroxy-ETE, and 12-oxoETE induced PMN Ca2+ transients and aggregation [respective potencies (5-hydroxy-ETE = 1) of 0.1, 0.01, and 0.003] but did not effect degranulation, and 15-hydroxy-ETE, 15-OxoETE, and 15-oxo-11-trans-ETE were inactive in all assays. Finally, 5-oxo/hydroxy-ETEs desensitized PMN to themselves but not to 12-oxo/hydroxy-ETEs or leukotriene (LT)B4; 12-oxo/hydroxy-ETEs and LTB4 desensitized PMN to themselves and each other but not to 5-oxo/hydroxy-ETEs; 15-oxo/hydroxy-ETEs did not desensitize PMN; and a LTB4 receptor antagonist blocked responses to LTB4 and 12-oxo/hydroxy-ETEs but not to 5-oxo/hydroxy-ETEs. Thus, 5-oxo/hydroxy-ETEs act by a common, LTB4 receptor-independent mechanism that recognizes 5- but not 12- or 15-oxo/hydroxy-ETEs and prefers oxo over hydroxy residues at C5 whereas 12-oxo/hydroxy-ETEs act via a LTB4 receptor mechanism that recognizes 12- but not 5- or 15-oxo/hydroxy-ETEs and prefers hydroxy over oxo residues at C12.