12(R)-HETE
(Synonyms: 12(R)-Hydroxyeicosatetraenoic Acid) 目录号 : GC40447An active metabolite of arachidonic acid
Cas No.:82337-46-0
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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Biosynthesis of 12(R)-HETE in invertebrates is via lipoxygenation of arachidonic acid . In mammals, 12(R)-HETE can be produced by 12(R)-LOs and also by CYP450 oxidation. The activity of 12(R)-HETE in mammals is predominantly proinflammatory. 12(R)-HETE exhibits dose-dependent leukocyte chemotaxis at concentrations as low as 100 nM, and lowers intraocular pressure in rabbits.
Cas No. | 82337-46-0 | SDF | |
别名 | 12(R)-Hydroxyeicosatetraenoic 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,DMF: Miscible,DMSO: Miscible,Ethanol: Miscible,PBS pH 7.2: 0.8 mg/ml | 储存条件 | Store at -20°C |
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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 |
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Metabolism of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) in corneal tissues: formation of novel metabolites
Arch Biochem Biophys 1991 Nov 1;290(2):326-35.PMID:1929401DOI:10.1016/0003-9861(91)90548-w.
12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric analysis as 8-hydroxy-4,6,10-hexadecatrienoic acid, the tetranor metabolite derived following two steps of beta-oxidation from the carboxy terminus. The beta-oxidation pathway was expressed in both microsomes and mitochondria isolated from bovine corneal epithelium and was dependent on the addition of oxidizing equivalents. The major metabolite of 12(R)-HETE in subcellular fractions of bovine corneal epithelial cells was a dihydro compound, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE). This derivative is presumably formed by an oxidation of the hydroxyl group followed by two keto-reduction steps, since its formation was accompanied by the appearance of a keto metabolite identified as 12-oxo-5,8,14-eicosatrienoic acid. The omega-hydroxylation, in contrast to other cell types, was a minor route for 12(R)-HETE metabolism in these tissues. Since 12(R)-HETE has been implicated as a modulator of Na(+)-K(+)-ATPase activity and its related functions in ocular tissues, these findings raise the possibility that the newly described metabolites may be involved in regulating corneal functions. In addition, the presence of a keto reductase in the cornea may be of great importance following injury since 12(R)-HETrE resulting from 12(R)-HETE by this activity is a potent ocular proinflammatory compound.
12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid derivative, is an activator of the aryl hydrocarbon receptor
Mol Pharmacol 2008 Dec;74(6):1649-56.PMID:18779363DOI:10.1124/mol.108.049379.
The aryl hydrocarbon receptor (AHR) is a ligand-regulated transcription factor that can be activated by structurally diverse chemicals, ranging from environmental carcinogens to dietary metabolites. Evidence supporting a necessary role for the AHR in normal biology has been established; however, identification of key endogenous ligand/activator remains to be established. Here, we report the ability of 12(R)-hydroxy-5(Z),8(Z),10(E), 14(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid metabolite produced by either a lipoxygenase or cytochrome P-450 pathway, to act as a potent indirect modulator of the AHR pathway. In contrast, structurally similar HETE isomers failed to demonstrate significant activation of the AHR. Electrophoretic mobility shift assays, together with ligand competition binding experiments, have demonstrated the inability of 12(R)-HETE to directly bind or directly activate the AHR to a DNA binding species in vitro. However, cell-based xenobiotic-responsive element-driven luciferase reporter assays indicate the ability of 12(R)-HETE to modulate AHR activity, and quantitation of induction of an AHR target gene confirmed 12(R)-HETE's ability to activate AHR-mediated transcription, even at high nanomolar concentrations in human hepatoma (HepG2)- and keratinocyte (HaCaT)-derived cell lines. One explanation for these results is that a metabolite of 12(R)-HETE is acting as a direct ligand for the AHR. However, several known metabolites failed to exhibit AHR activity. The ability of 12(R)-HETE to activate AHR target genes required receptor expression. These results indicate that 12(R)-HETE can serve as a potent activator of AHR activity and suggest that in normal and inflammatory disease conditions in skin, 12(R)-HETE is produced, perhaps leading to AHR activation.
Hormonal stimulation of 12(R)-HETE, a cytochrome P450 arachidonic acid metabolite in the rabbit cornea
Curr Eye Res 1990 Jul;9(7):661-7.PMID:2119938DOI:10.3109/02713689008999581.
12(R)-HETE [12(R)-hydroxy-5, 8, 10, 14 eicosatetraenoic acid] is one of the major arachidonic acid metabolites produced by microsomal cytochrome P450 of the corneal epithelium. This metabolite is a potent inhibitor of Na(+)-K(+)-ATPase activity in several tissues. We investigated endogenous production of 12(R)-HETE in the rabbit corneal epithelium. Incubation of corneal epithelial sheets (prelabeled with 14C-arachidonic acid) with arginine vasopressin resulted in the production of radioactive 12(R)-HETE suggesting its formation from endogenously labeled-arachidonic acid. The maximal response was obtained with 1 microM arginine vasopressin and represents a 15-fold increase in 12(R)-HETE formation compared with that of control tissues. Stimulation of 14C-arachidonic acid release with a detergent, digitonin, also resulted in endogenous 12(R)-HETE formation. Analysis of the incubation media following digitonin treatment of prelabeled corneal epithelial sheets revealed that 12(R)-HETE production was maximal at 20 microM digitonin, a 17-fold increase over control values. This study is the first to describe hormonal and traumatic stimulation of 12(R)-HETE formation from endogenously labeled arachidonic acid in intact corneal tissues. This study demonstrates that the formation of this Na(+)-K(+)-ATPase inhibitor can be modulated by physiological and pathophysiological regulation.
Modulation of vascular tone by 12(R)-, but not 12(S)-, hydroxyeicosatetraenoic acid
Eur J Pharmacol 1988 Jul 14;151(3):487-90.PMID:3215273DOI:10.1016/0014-2999(88)90549-3.
The vascular activity of the two stereoisomers of 12-hydroxyeicosatetraenoic acid (12-HETE) was assessed on rabbit thoracic aortic rings. In vessels contracted in K+-free media, 12(R)-HETE inhibited the relaxations produced by the addition of KCl, in a concentration-dependent manner, while 12(S)-HETE had little effect. 12(R)-HETE, but not the 12(S) isomer, potentiated phenylephrine-induced contractions of aortic rings in normal buffer. Thus 12(R)-HETE can modulate vascular tone, perhaps by inhibition of Na+,K+-ATPase activity.
A comparison of the proinflammatory effects of 12(R)- and 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid in human skin
Prostaglandins 1989 Oct;38(4):465-71.PMID:2813813DOI:10.1016/0090-6980(89)90129-9.
Topical application of racemic 12-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R,S)-HETE] produces erythema and leucocyte accumulation in human skin. Since 12(R)-HETE is more potent than its epimer 12(S)-HETE as a neutrophil chemoattractant in vitro, their proinflammatory effects have now been compared in vivo. 12(R)- and 12(S)-HETE (0.5 - 20 ug/site) were applied topically to the forearm skin of 5 healthy volunteers and the sites occluded for 6 h. Five ug each of the two enantiomers were also applied to the opposite forearm. At 6 and 24 h blood flow and the areas of erythematous responses were measured. The 5 ug application sites were biopsied at 24 h. Both enantiomers caused dose related erythema and increased blood flow at 6 and 24 h, which were not significantly different at either of the time points tested. In contrast, pronounced neutrophil infiltrates were seen in the epidermis (25.2 +/- 13 cells/hpf) and dermis (13.2 +/- 5.1 cells/hpf) 24 h after application of 12(R)-, but not 12(S)-HETE (0.02 +/- 0.02 and 1.02 +/- 0.7 cells/hpf in epidermis and dermis respectively). However, the numbers of dermal mononuclear cells accumulating in response to the two enantiomers were similar. 12(R)-HETE thus appears to be a more potent neutrophil chemoattractant than 12(S)-HETE in human skin in vivo and may be of potential importance as a mediator of inflammation in man.