MCTR3
(Synonyms: 13-cysteinyl14-hydroxyDocosahexaenoic Acid, Maresin Conjugates in Tissue Regeneration 3, Maresin Sulfido Conjugate 3) 目录号 : GC44140
A specialized pro-resolving mediator
Cas No.:1784701-63-8
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
Maresin conjugates in tissue regeneration 3 (MCTR3) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid in macrophages. DHA is oxidized to maresin 1 , which is converted to MCTR1 by glutathione S-transferase Mu 4 or leukotriene C4 synthase, then to MCTR2 by γ-glutamyl transferase, and to MCTR3 by dipeptidase. MCTR3 accelerates tissue regeneration in planaria (1 and 100 nM) approximately as potently as MCTR2 and more potently than MCTR1. Pretreatment with MCTR3 prior to E. coli administration in mice reduces neutrophil infiltration, shortens the inflammatory resolution period, and increases phagocytosis of E. coli by macrophages. When administered at a dose of 100 ng 12h post E. coli infection in a mouse model of peritonitis, MCTR3 selectively reduces the amount of the eicosanoids PGD2 , PGE2 , PGF2α , and TXB2 in the exudate.
| Cas No. | 1784701-63-8 | SDF | |
| 别名 | 13-cysteinyl14-hydroxyDocosahexaenoic Acid, Maresin Conjugates in Tissue Regeneration 3, Maresin Sulfido Conjugate 3 | ||
| Canonical SMILES | O[C@@H](C/C=C\C/C=C\CC)[C@H](SC[C@H](N)C(O)=O)/C=C/C=C/C=C\C/C=C\CCC(O)=O | ||
| 分子式 | C25H37NO5S | 分子量 | 463.6 |
| 溶解度 | EtOH/Water (95:5): 2 mg/ml,DMF: 50 mg/ml,DMSO: 50 mg/ml,Ethanol: 1 mg/ml,PBS (pH 7.2): 0.1 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 | 2.157 mL | 10.7852 mL | 21.5703 mL |
| 5 mM | 0.4314 mL | 2.157 mL | 4.3141 mL |
| 10 mM | 0.2157 mL | 1.0785 mL | 2.157 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。
MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway
Int Immunopharmacol 2021 Jan;90:107142.PMID:33268042DOI:10.1016/j.intimp.2020.107142.
Acute lung injury (ALI), a common respiratory distress syndrome in the intensive care unit (ICU), is mainly caused by severe infection and shock. Epithelial and capillary endothelial cell injury, interstitial edema and inflammatory cell infiltration are the main pathological changes observed in ALI animal models. Maresin conjugates in tissue regeneration (MCTR) are a new family of anti-inflammatory proteins. MCTR3 is a key enhancer of the host response, that promotes tissue regeneration and reduces infection; however, its role and mechanism in ALI are still unclear. The purpose of our research was to assess the protective effects of MCTR3 against ALI and its underlying mechanism. The work in this study was conducted in a murine model and the pulmonary epithelial cell line MLE-12. In vivo, MCTR3 (2 ng/g) was given 2 h after lipopolysaccharide (LPS) injection. We found that the treatment of mice with LPS-induced ALI with MCTR3 significantly reduced the cell number and protein levels in the bronchoalveolar lavage fluid (BALF); decreased the production of inflammatory cytokines; alleviated oxidative stress and cell apoptosis, consequently decreased lung injury; and restored pulmonary function. These protective effects of MCTR3 were dependent on down-regulation of the PTEN-induced putative kinase 1 (PINK1) pathway. Additionally, in MLE-12 cells stimulated with LPS, MCTR3 inhibited cell death, inflammatory cytokine levels and oxidative stress via the ALX/PINK1 signaling pathway. Thus, we conclude that MCTR3 protected against LPS-induced ALI partly through inactivation of the ALX/PINK1 mediated mitophagy pathway.
MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis
EBioMedicine 2022 May;79:103974.PMID:35430453DOI:10.1016/j.ebiom.2022.103974.
Background: Rheumatoid arthritis (RA) is a progressive degenerative disorder that leads to joint destruction. Available treatments only target the inflammatory component with minimal impact on joint repair. We recently uncovered a previously unappreciated family of pro-resolving mediators, the maresin conjugate in tissue regeneration (MCTR), that display both immunoregulatory and tissue-protective activities. Thus, we queried whether the production of these autacoids is disrupted in RA patients and whether they can be useful in treating joint inflammation and promoting joint repair. Methods: Using a highly phenotyped RA cohort we evaluated plasma MCTR concentrations and correlated these to clinical markers of disease activity. To evaluate the immunoregulatory and tissue reparative activities we employed both in vivo models of arthritis and organ culture models. Findings: Herein, we observed that plasma MCTR3 concentrations were negatively correlated with joint disease activity and severity in RA patients. Evaluation of the mechanisms engaged by this mediator in arthritic mice demonstrated that MCTR3 reprograms monocytes to confer enduring joint protective properties. Single cell transcriptomic profiling and flow cytometric evaluation of macrophages from mice treated with MCTR3-reprogrammed monocytes revealed a role for Arginase-1 (Arg-1) in mediating their joint reparative and pro-resolving activities. Arg-1 inhibition reversed both the anti-arthritic and tissue reparative actions of MCTR3-reprogrammed monocytes. Interpretation: Our findings demonstrate that circulating MCTR3 levels are negatively correlated with disease in RA. When administered to mice in vivo, MCTR3 displayed both anti-inflammatory and joint reparative activities, protecting both cartilage and bone in murine arthritis. These activities were, at least in part, mediated via the reprogramming of mononuclear phagocyte responses. Funding: This work was supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant no: 677542) and the Barts Charity (grant no: MGU0343) to J.D. J.D. is also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z).
Identification and Actions of a Novel Third Maresin Conjugate in Tissue Regeneration: MCTR3
PLoS One 2016 Feb 16;11(2):e0149319.PMID:26881986DOI:10.1371/journal.pone.0149319.
Maresin conjugates in tissue regeneration (MCTR) are a new family of evolutionarily conserved chemical signals that orchestrate host responses to promote tissue regeneration and resolution of infections. Herein, we identified the novel MCTR3 and established rank order potencies and matched the stereochemistries of MCTR1, MCTR2 and MCTR3 using material prepared by total organic synthesis and mediators isolated from both mouse and human systems. MCTR3 was produced from endogenous substrate by E. coli activated human macrophages and identified in sepsis patients. Each of the three synthetic MCTR dose-dependently (1-100 nM) accelerated tissue regeneration in planaria by 0.6-0.9 days. When administered at the onset or peak of inflammation, each of the MCTR promoted resolution of E. coli infections in mice. They increased bacterial phagocytosis by exudate leukocytes (~15-50%), limited neutrophil infiltration (~20-50%), promoted efferocytosis (~30%) and reduced eicosanoids. MCTR1 and MCTR2 upregulated human neutrophil and macrophage phagocytic responses where MCTR3 also proved to possess potent actions. These results establish the complete stereochemistry and rank order potencies for MCTR1, MCTR2 and MCTR3 that provide novel resolution moduli in regulating host responses to clear infections and promote tissue regeneration.
Cysteinyl-maresin 3 inhibits IL-13 induced airway hyperresponsiveness through alternative activation of the CysLT1 receptor
Eur J Pharmacol 2022 Nov 5;934:175257.PMID:36116518DOI:10.1016/j.ejphar.2022.175257.
Background: Cysteinyl-maresins, also known as maresin-conjugates in tissue regeneration (MCTRs), are recently discovered lipid mediators proposed to reduce airway inflammation. Objective: To investigate the influence of MCTRs on IL-13-induced airway hyperresponsiveness in isolated human and mice airways. Methods: Before responsiveness to contractile agonists were assessed in myographs, human small bronchi were cultured for 2 days and mouse tracheas were cultured for 1-4 days. During the culture procedure airways were exposed to interleukin (IL)-13 in the presence or absence of MCTRs. Signalling mechanisms were explored using pharmacologic agonists and antagonists, and genetically modified mice. Results: IL-13 treatment increased contractions to histamine, carbachol and leukotriene D4 (LTD4) in human small bronchi, and to 5-hydroxytryptamine (5-HT) in mouse trachea. In both preparations, co-incubation of the explanted tissues with MCTR3 reduced the IL-13 induced enhancement of contractions. In mouse trachea, this inhibitory effect of MCTR3 was blocked by three different CysLT1 receptor antagonists (montelukast, zafirlukast and pobilukast) during IL-13 exposure. Likewise, MCTR3 failed to reduce the IL-13-induced 5-HT responsiveness in mice deficient of the CysLT1 receptor. However, co-incubation with the classical CysLT1 receptor agonist LTD4 did not alter the IL-13-induced 5-HT hyperreactivity. Conclusions: MCTR3, but not LTD4, decreased the IL-13-induced airway hyperresponsiveness by activation of the CysLT1 receptor. The distinct actions of the two lipid mediators on the CysLT1 receptor suggest an alternative signalling pathway appearing under inflammatory conditions, where this new action of MCTR3 implicates potential to inhibit airway hyperresponsiveness in asthma.
Periodontal Stem Cells Synthesize Maresin Conjugate in Tissue Regeneration 3
J Dent Res 2022 Sep;101(10):1205-1213.PMID:PMC9403725DOI:10.1177/00220345221090879.
Periodontal disease is a significant public health problem worldwide. Excess unresolved chronic inflammation destroys the periodontal tissues that surround and support the teeth, and efforts to control inflammation by removal of bacterial deposits on the teeth have limited long-term impact. Likewise, procedures aimed at regeneration of the periodontal tissues have shown limited success. Recent advances in stem cell research have shown promising novel prospects for the use of periodontal ligament stem cells (PDLSCs) in tissue regeneration; however, control of inflammation remains a barrier. Human PDLSCs have been shown to release specialized proresolving lipid mediators (SPMs) that modulate the immune response and promote resolution of inflammation, tissue repair, and regeneration. Studies on stem cell biology in periodontology have also been limited by the lack of a good large animal model. Herein, we describe PDLSC biology of the Yorkshire pig (pPDLSCs). pPDLSCs were isolated and characterized. Using lipid mediator profiling, we demonstrate for the first time that pPDLSCs biosynthesize cysteinyl-containing SPMs (cys-SPMs), specifically, maresin conjugates in tissue regeneration 3 (MCTR3) and its authentication using liquid chromatography/tandem mass spectrometry. The exogenous addition of the n-3 precursor docosahexaenoic acid enhances MCTR3 biosynthesis. Using immunocytochemistry, we show that pPDLSCs express 4 of the SPM biosynthetic pathway enzymes necessary for SPM biosynthesis, including 5-lipoxygenase, 12-lipoxygenase, and 15-lipoxygenase-1. In addition, we identified and quantified the cytokine/chemokine profile of pPDLSCs using a 13-plex immunology multiplex assay and found that the pretreatment of pPDLSCs with MCTR3 in an inflammatory environment reduced the production of acute and chronic proinflammatory cytokines/chemokines. Together, these results suggest that enhancing resolution of inflammation pathways and mediators may be a possible key early event in predictable periodontal regeneration.