12(S)-HETE
(Synonyms: 12(S)-Hydroxyeicosatetraenoic Acid) 目录号 : GC40448The predominant lipoxygenase product of mammalian platelets
Cas No.:54397-83-0
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
12(S)-HETE is the predominant lipoxygenase product of mammalian platelets. [1] It enhances tumor cell adhesion to endothelial cells, fibronectin, and the subendothelial matrix at 0.1µM181M.[2][3]
Reference:
[1]. Hamberg, M., and Samuelsson, B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. U.S.A. 71(9), 3400-3404 (1974).
[2]. Grossi, I.M., Fitzgerald, L.A., Umbarger, L.A., et al. Bidirectional control of membrane expression and/or activation of the tumor cell IRGpIIb/IIIa receptor and tumor cell adhesion by lipoxygenase products of arachidonic acid and linoleic acid. Cancer Res. 49(4), 1029-1037 (1989).
[3]. Honn, K.V., Nelson, K.K., Renaud, C., et al. Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis. Prostaglandins 44(5), 413-429 (1992).
| Cas No. | 54397-83-0 | SDF | |
| 别名 | 12(S)-Hydroxyeicosatetraenoic Acid | ||
| 化学名 | 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid | ||
| Canonical SMILES | CCCCC/C=C\C[C@H](O)/C=C/C=C\C/C=C\CCCC(O)=O | ||
| 分子式 | C20H32O3 | 分子量 | 320.5 |
| 溶解度 | <0.1 M Na2CO3: 2 mg/ml; PBS pH 7.2: 0.8 mg/ml; Miscible in DMF; Miscible in DMSO; Miscible in Ethanol | 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 | 3.1201 mL | 15.6006 mL | 31.2012 mL |
| 5 mM | 0.624 mL | 3.1201 mL | 6.2402 mL |
| 10 mM | 0.312 mL | 1.5601 mL | 3.1201 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。
Macrophage 12(S)-HETE Enhances Angiotensin II-Induced Contraction by a BLT2 (Leukotriene B4 Type-2 Receptor) and TP (Thromboxane Receptor)-Mediated Mechanism in Murine Arteries
Hypertension 2022 Jan;79(1):104-114.PMID:34784723DOI:10.1161/HYPERTENSIONAHA.121.17824.
12/15-LO (12/15-lipoxygenase), encoded by Alox15 gene, metabolizes arachidonic acid to 12(S)-HETE (12-hydroxyeicosatetraenoic acid). Macrophages are the major source of 12/15-LO among immune cells, and 12/15-LO plays a crucial role in development of hypertension. Global Alox15- or macrophage-deficient mice are resistant to Ang II (angiotensin II)-induced hypertension. This study tests the hypothesis that macrophage 12(S)-HETE contributes to Ang II-mediated arterial constriction and thus to development of Ang II-induced hypertension. Ang II constricted isolated abdominal aortic and mesenteric arterial rings. 12(S)-HETE (100 nmol/L) alone was without effect; however, it significantly enhanced Ang II-induced constriction. The presence of wild-type macrophages also enhanced the Ang II-induced constriction, while Alox15-/- macrophages did not. Using this model, pretreatment of aortic rings with inhibitors, receptor agonists/antagonists, or removal of the endothelium, systematically uncovered an endothelium-mediated, Ang II receptor-2-mediated and superoxide-mediated enhancing effect of 12(S)-HETE on Ang II constrictions. The role of superoxide was confirmed using aortas from p47phox-/- mice where 12(S)-HETE failed to enhance constriction to Ang II. In cultured arterial endothelial cells, 12(S)-HETE increased the production of superoxide, and 12(S)-HETE or Ang II increased the production of an isothromboxane-like metabolite. A TP (thromboxane receptor) antagonist inhibited 12(S)-HETE enhancement of Ang II constriction. Both Ang II-induced hypertension and the enhancing effect of 12(S)-HETE on Ang II contractions were eliminated by a BLT2 (leukotriene B4 receptor-2) antagonist. These results outline a mechanism where the macrophage 12/15-LO pathway enhances the action of Ang II. 12(S)-HETE, acting on the BLT2, contributes to the hypertensive action of Ang II in part by promoting endothelial synthesis of a superoxide-derived TP agonist.
12-lipoxygenases and 12(S)-HETE: role in cancer metastasis
Cancer Metastasis Rev 1994 Dec;13(3-4):365-96.PMID:7712597DOI:10.1007/BF00666105.
Arachidonic acid metabolites have been implicated in multiple steps of carcinogenesis. Their role in tumor cell metastasis, the ultimate challenge for the treatment of cancer patients, are however not well-documented. Arachidonic acid is primarily metabolized through three pathways, i.e., cyclooxygenase, lipoxygenase, and P450-dependent monooxygenase. In this review we focus our attention on one specific lipoxygenase, i.e., 12-lipoxygenase, and its potential role in modulating the metastatic process. In mammalian cells there exist three types of 12-lipoxygenases which differ in tissue distribution, preferential substrates, and profile of their metabolites. Most of these 12-lipoxygenases have been cloned and sequenced, and the molecular and biochemical determinants responsible for catalysis of specific substrates characterized. Solid tumor cells express 12-lipoxygenase mRNA, possess 12-lipoxygenase protein, and biosynthesize 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid], as revealed by numerous experimental approaches. The ability of tumor cells to generate 12(S)-HETE is positively correlated to their metastatic potential. A large collection of experimental data suggest that 12(S)-HETE is a crucial intracellular signaling molecule that activates protein kinase C and mediates the biological functions of many growth factors and cytokines such as bFGF, PDGF, EGF, and AMF. 12(S)-HETE plays a pivotal role in multiple steps of the metastatic 'cascade' encompassing tumor cell-vasculature interactions, tumor cell motility, proteolysis, invasion, and angiogenesis. The fact that 12-lipoxygenase is expressed in a wide diversity of tumor cell lines and 12(S)-HETE is a key modulatory molecule in metastasis provides the rationale for targeting these molecules in anti-cancer and anti-metastasis therapeutic protocols.
Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages
J Lipid Res 2018 Apr;59(4):615-624.PMID:29472381DOI:10.1194/jlr.M081448.
Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction. Cultured M2 macrophages metabolized externally added [14C]12(S)-HETE into more polar metabolites, while M1 macrophages had little effect on the catabolism. The major metabolites were identified by mass spectrometry as (ω-1)-hydroxylation and β-oxidation products. The conversion was inhibited by both peroxisomal β-oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1) and peroxisomal β-oxidation markers were upregulated upon M2 polarization. The identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10-hexadecadienoic acid metabolites were tested on abdominal aortic rings for biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin II from 15% to 25%, the metabolites did not. These results indicate that M2, but not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the angiotensin II-induced vascular constriction, supporting a possible antihypertensive role of M2 macrophages.
Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)-HETE-induced endothelial cell retraction
FASEB J 1989 Sep;3(11):2285-93.PMID:2673900DOI:10.1096/fasebj.3.11.2673900.
A 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE), which is produced by platelets and tumor cells, was tested for its ability to induce retraction of endothelial cell monolayers. The induction of endothelial cell retraction is a critical step in tumor cell metastasis. Endothelial cells demonstrated reversible retraction in response to 12(S)-HETE, but did not respond to the stereoisomer 12(R)-HETE or to unrelated 5-lipoxygenase (i.e., 5[S]-HETE) or 15-lipoxygenase (i.e., 15[S]-HETE) metabolites. Endothelial cells did not demonstrate loss of viability in response to 12(S)-HETE. The induction of retraction was both dose and time dependent. Scanning electron microscopy confirmed that 12(S)-HETE induced endothelial cell retraction and revealed collapsed filopodia on their surface, the appearance of spaces between endothelial cells and the underlying subendothelial matrix, in addition to large gaps between adjacent endothelial cells. Tumor cell adhesion to endothelial cell monolayers was enhanced 1 h after pretreatment of monolayers with 12(S)-HETE but not after pretreatment with other lipoxygenase metabolites. Tumor cell adhesion to endothelial cell monolayers 36 h after pretreatment with 12(S)-HETE was not different from adhesion to untreated monolayers. Therefore we suggest that 12(S)-HETE generated during tumor cell-platelet-endothelial cell interactions may induce reversible endothelial cell retraction, allowing tumor cell access to the subendothelial matrix, which is a critical step in their eventual extravasation from the microvasculature during hematogenous metastasis.
Endothelial 12(S)-HETE vasorelaxation is mediated by thromboxane receptor inhibition in mouse mesenteric arteries
Am J Physiol Heart Circ Physiol 2013 Feb 1;304(3):H382-92.PMID:23203967DOI:10.1152/ajpheart.00690.2012.
Arachidonic acid (AA) metabolites mediate endothelium-dependent relaxation in many vascular beds. Previously, we identified the major AA 12/15-lipoxygenase (12/15-LO) metabolite of mouse arteries as 12-hydroxyeicosatetraenoic acid (12-HETE). The goal was to determine the stereospecific configuration of mouse vascular 12-HETE and characterize the role of 12-HETE stereoisomers in the regulation of vascular tone. Using normal, reverse phase, and chiral HPLC, the stereospecific configuration was identified as 12(S)-HETE. 12(S)-HETE relaxed U46619-, carbocyclic thromboxane A(2)-, PGF(2α)-, and 8-iso PGF(2α)-preconstricted mesenteric arteries, but not phenylephrine-preconstricted arteries. 12(R)-HETE was more potent than 12(S)-HETE in relaxing U46619-preconstricted mouse arteries (maximum relaxations = 91.4 ± 2.7% and 71.8 ± 5.9%, respectively). Neither 12-HETE isomer caused constriction. Pretreatment with 12(S)- or 12(R)-HETE (1 μM) inhibited constrictions to U46619 but not phenylephrine. To investigate the role of thromboxane A(2) (TP) receptors in 12-HETE vascular actions, [(3)H]SQ29548 radioligand binding studies were performed in mouse platelets. U46619, 12(R)-HETE, and 12(S)-HETE displaced [(3)H]SQ29548 binding with IC(50)s of 0.07, 0.32, and 1.73 μM, respectively. Both 12(S)- and 12(R)-HETE inhibited intracellular calcium increases induced by U46619 (10 nM) in HEK293 cells overexpressing TP(α) receptor (65.5% and 45.1%, respectively) and coexpressing prostacyclin (IP) and TP(α) receptors (58.0% and 27.1%, respectively). The LO inhibitor NDGA (10 μM) reduced AA relaxations in arteries preconstricted with U46619 but not phenylephrine. These results indicate that exogenous and endogenous 12(S)-HETE relax mouse mesenteric arteries that are preconstricted with thromboxane agonists. These 12(S)-HETE relaxations are mediated by TP receptor competitive inhibition and inhibition of TP agonist-induced increases in intracellular calcium.