10-Nitrooleate
(Synonyms: 10-硝基油酸,CXA-10) 目录号 : GC41868A novel endogenous lipid signalling molecule
Cas No.:875685-46-4
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
Nitrated unsaturated fatty acids, such as 10- and 12-nitrolinoleate , cholesteryl nitrolinoleate, and nitrohydroxylinoleate, represent a new class of endogenous lipid-derived signalling molecules. LNO2 isomers serve as potent endogenous ligands for PPARγ and can also decompose or be metabolized to release nitric oxide. 10-Nitrooleate is one of two regioisomers of nitrooleate, the other being 9-nitrooleate (OA-NO2; used for the mixture of isomers), which are formed by nitration of oleic acid in approximately equal proportions in vivo. Peroxynitrite, acidified nitrite, and myeloperoxidase in the presence of H2O2 and nitrite, all mediate the nitration of oleic acid. OA-NO2 is found in human plasma as the free acid and esterified in phospholipids at concentrations of 619 ± 52 nM and 302 ± 369 nM, respectively. OA-NO2 activates PPARγ approximately 7-fold at a concentration of 1 µM and effectively promotes differentiation 3T3-L1 preadipocytes to adipocytes at 3 µM.
| Cas No. | 875685-46-4 | SDF | |
| 别名 | 10-硝基油酸,CXA-10 | ||
| Canonical SMILES | CCCCCCCC/C([N+]([O-])=O)=C\CCCCCCCC(O)=O | ||
| 分子式 | C18H33NO4 | 分子量 | 327.5 |
| 溶解度 | Ethanol: 1 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 | 3.0534 mL | 15.2672 mL | 30.5344 mL |
| 5 mM | 0.6107 mL | 3.0534 mL | 6.1069 mL |
| 10 mM | 0.3053 mL | 1.5267 mL | 3.0534 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。
Nitrated fatty acid, 10-Nitrooleate protects against hyperoxia-induced acute lung injury in mice
Int Immunopharmacol 2022 Aug;109:108838.PMID:35561478DOI:10.1016/j.intimp.2022.108838.
The antioxidant and anti-inflammatory effects of electrophilic nitrated fatty acid (NFA); 10-Nitrooleate, have been reported. The present study investigated whether 10-Nitrooleate has a protective role against hyperoxic-induced acute lung injury (HALI). Using a C57BL/6 mice model of HALI, we investigated the protective effect of 10-Nitrooleate. C57BL/6 mice were administered with NFA intratracheally, exposed to hyperoxia for 48 h to induce HALI, and kept at room air for 24 h. Bronchoalveolar lavage (BAL) fluid and lung samples were collected after 24 h of post hyperoxia to analyze markers associated with HALI. Intratracheal (IT) and intraperitoneal (IP) administration of NFA notably attenuated hyperoxia-induced infiltration of inflammatory cells, alveolar-capillary leakage, upregulation of proinflammatory cytokine levels (IL-6 and TNFα) into the BAL fluid, and resolution of inflammation in the lung. Western blot analyses showed that 10-Nitrooleate reduced the expression of the inflammatory transcription factor NFκB p65 subunit and increased antioxidant proteins HO-1 and NQO1 expression in the lung tissues compared to vehicle-treated animals. Moreover, 10-Nitrooleate reversed the hyperoxia-induced expression of mitophagy-associated markers (PINK1 and p62/SQSTM1), thereby protecting the HALI/ acute respiratory distress syndrome (ARDS). IT and IP delivery of 10-Nitrooleate reduces hyperoxia-induced ALI/ARDS by regulating the antioxidant pathways and restoring the mitochondrial homeostasis by regulating mitophagy. It is suggested that NFAs can be further evaluated as supplementary therapy for critically ill patients like COVID-19/ARDS.
The nitrated fatty acid, 10-Nitrooleate inhibits the neutrophil chemotaxis via peroxisome proliferator-activated receptor gamma in CLP-induced sepsis in mice
Int Immunopharmacol 2019 Jul;72:159-165.PMID:30981081DOI:10.1016/j.intimp.2019.04.001.
The inhibition of polymorphonuclear neutrophils' (PMNs) migration to the source of injury is among the most prominent aspects of immunosuppression following sepsis, although the precise mechanisms involved remain unclear and multifaceted. Increasing evidence connects this immunosuppression to nitric oxide (NO), as NO production is a classic feature of inflammation probably through neutrophil activation and migration. Nitrated fatty acids (NFA) such as 10-Nitrooleate (OA-NO2), nitrolinoleic acid etc. produced endogenously by the non-enzymatic reaction of NO with unsaturated fatty acids, are found to be potent activators of the transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ). Upregulation of PPARγ during immunosuppression and the subsequent inhibition of neutrophil migration in sepsis have been reported. However, the interplay of OA-NO2, NO and PPARγ in polymicrobial-induced immunosuppression has not been established. Hence to understand this, we have studied the role of OA-NO2 in blood PMNs migration, the effects of iNOS inhibitor on PMNs migration and PPARγ activity in cecal ligation and puncture (CLP)-induced sepsis in mice. We found increased expression of PPARγ and its DNA-binding activity in the lungs and blood PMNs from CLP mice. CLP or OA-NO2 treatment inhibited PMNs' migration in response to fMLP stimulation. Pharmacological inhibition of iNOS resulted in decreased PPARγ DNA-binding activity with a concomitant increase in the migration of PMNs to the site of infection. OA-NO2 treatment also inhibited the production of inflammatory cytokines (TNFα and IL-1β) secretion from PMNs stimulated with lipopolysaccharide. We have also established that, OA-NO2 mediated inhibition of PMNs migration in vivo and ex vivo are regulated through PPARγ-dependent pathway. This study further highlights the fact that the activation of PPARγ by the NFA has a pivotal role in PMNs' migration and immunosuppression.
Oxylipin Profiling of Alzheimer's Disease in Nondiabetic and Type 2 Diabetic Elderly
Metabolites 2019 Sep 5;9(9):177.PMID:31491971DOI:10.3390/metabo9090177.
Oxygenated lipids, called "oxylipins," serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer's disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-Nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD.
Regulation of human mitochondrial aldehyde dehydrogenase (ALDH-2) activity by electrophiles in vitro
J Biol Chem 2011 Mar 18;286(11):8893-900.PMID:21252222DOI:10.1074/jbc.M110.190017.
Recently, mitochondrial aldehyde dehydrogenase (ALDH-2) was reported to reduce ischemic damage in an experimental myocardial infarction model. ALDH-2 activity is redox-sensitive. Therefore, we here compared effects of various electrophiles (organic nitrates, reactive fatty acid metabolites, or oxidants) on the activity of ALDH-2 with special emphasis on organic nitrate-induced inactivation of the enzyme, the biochemical correlate of nitrate tolerance. Recombinant human ALDH-2 was overexpressed in Escherichia coli; activity was determined with an HPLC-based assay, and reactive oxygen and nitrogen species formation was determined by chemiluminescence, fluorescence, protein tyrosine nitration, and diaminonaphthalene nitrosation. The organic nitrate glyceryl trinitrate caused a severe concentration-dependent decrease in enzyme activity, whereas incubation with pentaerythritol tetranitrate had only minor effects. 4-Hydroxynonenal, an oxidized prostaglandin J(2), and 9- or 10-Nitrooleate caused a significant inhibition of ALDH-2 activity, which was improved in the presence of Mg(2+) and Ca(2+). Hydrogen peroxide and NO generation caused only minor inhibition of ALDH-2 activity, whereas peroxynitrite generation or bolus additions lead to severe impairment of the enzymatic activity, which was prevented by the thioredoxin/thioredoxin reductase (Trx/TrxR) system. In the presence of glyceryl trinitrate and to a lesser extent pentaerythritol tetranitrate, ALDH-2 may be switched to a peroxynitrite synthase. Electrophiles of different nature potently regulate the enzymatic activity of ALDH-2 and thereby may influence the resistance to ischemic damage in response to myocardial infarction. The Trx/TrxR system may play an important role in this process because it not only prevents inhibition of ALDH-2 but is also inhibited by the ALDH-2 substrate 4-hydroxynonenal.
Allosteric Regulation of the Soluble Epoxide Hydrolase by Nitro Fatty Acids: a Combined Experimental and Computational Approach
J Mol Biol 2022 Sep 15;434(17):167600.PMID:35460669DOI:10.1016/j.jmb.2022.167600.
The human soluble epoxide hydrolase (hsEH) is a key regulator of epoxy fatty acid (EpFA) metabolism. Inhibition of sEH can maintain endogenous levels of beneficial EpFAs and reduce the levels of their corresponding diol products, thus ameliorating a variety of pathological conditions including cardiovascular, central nervous system and metabolic diseases. The quest for orthosteric drugs that bind directly to the catalytic crevice of hsEH has been prolonged and sustained over the past decades, but the disappointing outcome of clinical trials to date warrants alternative pharmacological approaches. Previously, we have shown that hsEH can be allosterically inhibited by the endogenous electrophilic lipid 15-deoxy-Δ12,14-Prostaglandin-J2, via covalent adduction to two cysteines, C423 and C522. In this study, we explore the properties and behaviour of three electrophilic lipids belonging to the class of the nitro fatty acids, namely 9- and 10-Nitrooleate and 10-nitrolinoleate. Biochemical and biophysical investigations revealed that, in addition to C423 and C522, nitro fatty acids can covalently bind to additional nucleophilic residues in hsEH C-terminal domain (CTD), two of which predicted in this study to be latent allosteric sites. Systematic mapping of the protein mutational space and evaluation of possible propagation pathways delineated selected residues, both in the allosteric patches and in other regions of the enzyme, envisaged to play a role in allosteric signalling. The responses elicited by the ligands on the covalent adduction sites supports future fragment-based design studies of new allosteric effectors for hsEH with increased efficacy and selectivity.