20-HETE
(Synonyms: 20-羟基二十碳-5Z,8Z,11Z,14Z-四烯酸) 目录号 : GC35075A cytochrome P450 (CYP450) metabolite of arachidonic acid
Cas No.:79551-86-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
20-
20-HETE是一种被认为在肾脏和脑血管中发挥自分泌作用的细胞色素P450（CYP450）代谢产物。在大鼠脑微血管中，20-HETE是一种血管收缩剂，介导压力诱导的自主调节血管收缩。20-HETE主要以葡萄糖醛酸结合物的形式排泄。游离20-HETE的浓度（人尿液中20-40 pg/ml）约为20-葡萄糖醛酸酯的浓度的10倍。20-HETE可以被环氧合酶进一步代谢为20-羟基PGG2和20-羟基PGH2。
1.McGiff, J.C., and Quilley, J.20-HETE and the kidney: Resolution of old problems and new beginningsAm. J. Physiol.277(3)R607-R623(1999) 2.Gebremedhin, D., Lange, A.R., Lowry, T.F., et al.Production of 20-HETE and its role in autoregulation of cerebral blood flowCirc. Res.87(1)60-65(2000) 3.Prakash, C., Zhang, J.Y., Falck, J.R., et al.20-Hydroxyeicosatetraenoic acid is excreted as a glucuronide conjugate in human urineBiochem. Biophys. Res. Commun.185(2)728-733(1992) 4.Schwartzman, M.L., Falck, J.R., Yadagiri, P., et al.Metabolism of 20-hydroxyeicosatetraenoic acid by cyclooxygenase. Formation and identification of novel endothelium-dependent vasoconstrictor metabolitesJ. Biol. Chem.264(20)11658-11662(1989)
| Cas No. | 79551-86-3 | SDF | |
| 别名 | 20-羟基二十碳-5Z,8Z,11Z,14Z-四烯酸 | ||
| Canonical SMILES | O=C(O)CCC/C=C\C/C=C\C/C=C\C/C=C\CCCCCO | ||
| 分子式 | C20H32O3 | 分子量 | 320.47 |
| 溶解度 | 0.1 M Na2CO3: 2 mg/ml ;DMF: Miscible ;DMSO: Miscible;Ethanol: Miscible;PBS pH 7.2: 0.8 mg/ml | 储存条件 | Store at -20°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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.1204 mL | 15.6021 mL | 31.2042 mL |
| 5 mM | 0.6241 mL | 3.1204 mL | 6.2408 mL |
| 10 mM | 0.312 mL | 1.5602 mL | 3.1204 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。
The CYP/20-HETE/GPR75 axis in hypertension
Adv Pharmacol 2022;94:1-25.PMID:35659370DOI:10.1016/bs.apha.2022.02.003.
20-Hydroxyeicosatetraenoic acid (20-HETE) is a bioactive lipid generated from the ω-hydroxylation of arachidonic acid (AA) by enzymes of the cytochrome P450 (CYP) family, primarily the CYP4A and CYP4F subfamilies. 20-HETE is most notably identified as a modulator of vascular tone, regulator of renal function, and a contributor to the onset and development of hypertension and cardiovascular disease. 20-HETE-mediated signaling promotes hypertension by sensitizing the vasculature to constrictor stimuli, inducing endothelial dysfunction, and potentiating vascular inflammation. These bioactions are driven by the activation of the G-protein coupled receptor 75 (GPR75), a 20-HETE receptor (20HR). Given the capacity of 20-HETE signaling to drive pro-hypertensive mechanisms, the CYP/20-HETE/GPR75 axis has the potential to be a significant therapeutic target for the treatment of hypertension and cardiovascular diseases associated with increases in blood pressure. In this chapter, we review 20-HETE-mediated cellular mechanisms that promote hypertension, highlight important data in humans such as genetic variants in the CYP genes that potentiate 20-HETE production and describe recent findings in humans with 20HR/GPR75 mutations. Special emphasis is given to the 20HR and respective receptor blockers that have the potential to pave a path to translational and clinical studies for the treatment of 20-HETE-driven hypertension, and obesity/metabolic syndrome.
20-HETE in neovascularization
Prostaglandins Other Lipid Mediat 2012 Aug;98(3-4):63-8.PMID:22227460DOI:10.1016/j.prostaglandins.2011.12.005.
Cytochrome P450 4A/F (CYP4A/F) converts arachidonic acid (AA) to 20-HETE by ω-hydroxylation. The contribution of 20-HETE to the regulation of myogenic response, blood pressure, and mitogenic actions has been well summarized. This review focuses on the emerging role of 20-HETE in physiological and pathological vascularization. 20-HETE has been shown to regulate vascular smooth muscle cells (VSMC) and endothelial cells (EC) by affecting their proliferation, migration, survival, and tube formation. Furthermore, the proliferation, migration, secretion of proangiogenic molecules (such as HIF-1α, VEGF, SDF-1α), and tube formation of endothelial progenitor cells (EPC) are stimulated by 20-HETE. These effects are mediated through c-Src- and EGFR-mediated downstream signaling pathways, including MAPK and PI3K/Akt pathways, eNOS uncoupling, and NOX/ROS system activation. Therefore, the CYP4A/F-20-HETE system may be a therapeutic target for the treatment of abnormal angiogenic diseases.
20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (Gq) to Affect Vascular Function and Trigger Hypertension
Circ Res 2017 May 26;120(11):1776-1788.PMID:28325781DOI:10.1161/CIRCRESAHA.116.310525.
Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases. Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists. The present study was undertaken to identify a receptor to which 20-HETE binds and through which it activates a signaling cascade that culminates in many of the functional outcomes attributed to 20-HETE in vitro and in vivo. Methods and results: Using crosslinking analogs, click chemistry, binding assays, and functional assays, we identified G-protein receptor 75 (GPR75), currently an orphan G-protein-coupled receptor (GPCR), as a specific target of 20-HETE. In cultured human endothelial cells, 20-HETE binding to GPR75 stimulated Gαq/11 protein dissociation and increased inositol phosphate accumulation and GPCR-kinase interacting protein-1-GPR75 binding, which further facilitated the c-Src-mediated transactivation of epidermal growth factor receptor. This results in downstream signaling pathways that induce angiotensin-converting enzyme expression and endothelial dysfunction. Knockdown of GPR75 or GPCR-kinase interacting protein-1 prevented 20-HETE-mediated endothelial growth factor receptor phosphorylation and angiotensin-converting enzyme induction. In vascular smooth muscle cells, GPR75-20-HETE pairing is associated with Gαq/11- and GPCR-kinase interacting protein-1-mediated protein kinase C-stimulated phosphorylation of MaxiKβ, linking GPR75 activation to 20-HETE-mediated vasoconstriction. GPR75 knockdown in a mouse model of 20-HETE-dependent hypertension prevented blood pressure elevation and 20-HETE-mediated increases in angiotensin-converting enzyme expression, endothelial dysfunction, smooth muscle contractility, and vascular remodeling. Conclusions: This is the first report to identify a GPCR target for an eicosanoid of this class. The discovery of 20-HETE-GPR75 pairing presented here provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases.
20-HETE in the regulation of vascular and cardiac function
Pharmacol Ther 2018 Dec;192:74-87.PMID:30048707DOI:10.1016/j.pharmthera.2018.07.004.
20-HETE, the ω-hydroxylation product of arachidonic acid catalyzed by enzymes of the cytochrome P450 (CYP) 4A and 4F gene families, is a bioactive lipid mediator with potent effects on the vasculature including stimulation of smooth muscle cell contractility, migration and proliferation as well as activation of endothelial cell dysfunction and inflammation. Clinical studies have shown elevated levels of plasma and urinary 20-HETE in human diseases and conditions such as hypertension, obesity and metabolic syndrome, myocardial infarction, stroke, and chronic kidney diseases. Studies of polymorphic associations also suggest an important role for 20-HETE in hypertension, stroke and myocardial infarction. Animal models of increased 20-HETE production are hypertensive and are more susceptible to cardiovascular injury. The current review summarizes recent findings that focus on the role of 20-HETE in the regulation of vascular and cardiac function and its contribution to the pathology of vascular and cardiac diseases.
Conflicting Roles of 20-HETE in Hypertension and Stroke
Int J Mol Sci 2019 Sep 11;20(18):4500.PMID:31514409DOI:10.3390/ijms20184500.
Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.