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Specific high-affinity bonding sites for the eicosanoid 12-hydroxy-5,8,10,14-eicosatetraenoic acid [12-HETE] in Lewis lung carcinoma cells contain specific high-affinity binding sites for the eicosanoid 12-hydroxy-5,8,10,14-eicosacetatetraenoic acid [12-HETE]. In the presence of 12-HETE, we present results revealing that the 50-kDa 12-HETE binding protein acts as a homodimer with steroid receptor coactivator-1. One of these was within the nuclear receptor interaction domain of SRC-1, which is responsible for binding of various steroid and thyroid hormone receptors. It contains the most C-terminal of the three versions of the LXXLL motif found in the nuclear receptor interaction domain. Although GST/SRC-1 1–1138 ligand-dependently removed a protein of 50 kDa in size, results from experiments and far Western analysis revealed that the N-terminal region of SRC-1 alone does not bind the 50-kDa 12-HETE binding protein, as well as far Western studies revealed that the protein in the 50-kDa bond protein alone did not bind the 50-kDa binding protein, whereas the protein of 50 ligand ligand-dependently bound protein in size, ligand kDa pulldown results revealed that ligand distant region of SRC-1 bindse binding protein in size showed that does not bind the 50 kDa binding protein, kDa binding protein, bindse binding protein, bindse binding protein, bindse binding protein alone does not kDa bindse binding protein of ligand far Western studies and far Western results and far Western binds, kDa Our findings show that the 50-kDa 12-HETE binding protein is a receptor that can promote signaling by contact with a nuclear receptor coactivator protein.
Source link: https://doi.org/10.1073/pnas.97.11.5779
[12-HETE] and 13-hydroxymethyl acid [13-HODE] in murine B16 amelanotic melanoma cells by the monohydroxy fatty acids 12-hydroxyeristotarenoic acid [12-HETE] and 13-hydroxyoctadecadienoic acid [13-HODE]. PKC-alpha transfer from the plasma membrane and focal adhesion plaques was carried out by HETE, contributing to increased adhesion of B16a cells to the matrix protein fibrin. In B16a cells, first, 12-HETE initiated a rapid rise in cellular levels of diacylglycerol and inositol trisphosphate. By 13-HODE, a high-affinity binding site for 12-HETE was discovered in B16a cells, and binding of 12-HETE to B16a cells was effectively blocked by 13-HODE.
Source link: https://doi.org/10.1073/pnas.92.20.9323
The thromboxane A 2 via cyclooxygenase process is well established; however, the role of 12-HETE via 12-lipoxygenase is little understood. Therefore, we used OPC-29030, a novel specific inhibitor of 12-HETE synthesis, to determine whether platelet-derived 12-HETE is involved in mediating cyclic flow variations and platelet aggregation in stenosed and endothelium-injured canine coronary arteries. Methods and Results — Since establishing CFVs, dogs were sent a vehicle or OPC-29030 intravenously. OPC-29030 restored CFVs in connection with rises in plasma and intraplatelet 12-HETE levels in association with rises in plasma and intraplatelet 12-HETE levels. The ADP- and U46619-induced rises in ex vivo platelet 12-HETE production and aggregation were both muzzled significant after the OPC-2903030 administration. Platelet aggregation was linearly related to platelet 12-HETE production. Human platelet glycoprotein IIb/IIIa can be activated by OPC-29030, but not IIIa. In vitro, OPC-29030 inhibited human platelet glycoprotein IIb/IIIa production.
Source link: https://doi.org/10.1161/01.cir.98.25.2891
In normal and streptozotocin-induced diabetic rats, we have investigated the effects of both prostacyclin and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid. 12-HETE is not only a potent censor of basal renin secrecy but also a key facilitator of ANG II-induced renin inhibition. In addition, we have investigated the effects of ANG II on 12-HETE formation in normal and diabetic rabbits. However, ANG II did not achieve an exaggerated rise in 12-HETE in diabetic renal tissue, despite the fact that ANG II did not have an exaggerated rise in 12-HETE. Insulin inhibited the inhibitory effects of ANG II on renin in normal rats, but it reduced the effect of ANG II in diabetic rats. Although renal cortical tissue's ability to synthesize 12-HETE in response to ANG II is unchanged, 12-HETE and ANG II actions are exaggerated in diabetes, contributing to reduced renin production.
Source link: https://doi.org/10.2337/diab.44.3.321
When 12-HETE synthesis was stimulated by thrombin or collagen, diabetic platesletlets synthesized significantly higher quantities of 12-HETE than did platelets from control subjects, whether or not there was in the presence or absence of indomethacin. When compared to platelets from the control subjects, Vitamin E content in platelets from the diabetic patients was dramatically reduced in platelets from the diabetic patients, but plasma vitamin E levels were not significantly different between the two groups. Low vitamin E intake and increased 12-HETE synthesis in platelets from type I diabetic patients, as shown by the above results.
Source link: https://doi.org/10.2337/diab.34.6.526
Pseudomonas aeruginosa's refined glycolipids contributed to the formation of significant quantities of 12-hydroxyeicosatetraenoic acid and serotonin in human platelets. Serotonin release was found at glycolipid levels above 5 micrograms/ml and increased dose-dependently to 100% at glycolipid concentrations above 40 micrograms/ml. At a glycolipid concentration of 50 micrograms/ml, optimum 12-HETE formation was obtained; higher amounts of glycolipid led to a decrease in 12-HETE formation, leading to a decrease in 12-HETE formation, which demonstrates a cytotoxic effect.
Source link: https://doi.org/10.1128/iai.60.8.3150-3155.1992
Since ciclosporin has therapeutic properties in chronic inflammatory dermatoses such as psoriasis or atopic eczema, we investigated the drug's effect on human keratinocyte binding to human keratinocytes. In comparison, pretreatment of epidermal cells for 24 h resulted in a dose-dependent decrease in specific 12-HETE binding, which was not seen in ciclosporin concentrations between 10-10 and 10 -6 M. The decrease of 12-HETE binding sites by ciclosporin, according to the study of saturation curves, the inhibition of 12-HETE binding by ciclosporin was owing to the reduction of 12-HETE binding sites, while receptor affinity remained unchanged.
Source link: https://doi.org/10.1159/000210961
In a murine skin inflammation model, the lipoxygenase inhibitor 2-phenylmethyl-1-naphthol has been shown to be a strong anti-inflammatory drug. Since 12-HETE is believed to have a pathophysiological function in inflammatory skin diseases, and epidermal cells have high affinity binding sites for 12-HETE, we investigated the effect of DuP 654 on 6-HETE binding to the human epidermal cell line SCL-II.
Source link: https://doi.org/10.1159/000211099
In a Chinese hamster fibroblast cell line overexpressing the rat vascular type-1a angiotensin II receptor, an influence of 12-hydroxyeicosatetraenoic acid, an arachidonic acid metabolite 12-lipoxygenase, was investigated by the p21Rac/Cdc42-activated kinase. 12-HETE's stimulatory activity on PAK1 development was dose-dependent, with maximum activation reaching 0. 01 M. In addition, transfection of dominant negative Cdc42 and Rac1 has stymied 12-HETE-induced PAK1, effectively ending 12-HETE-induced PAK1, implying that Cdc42 and Rac1 are the upstream initiators of 12-HETE-induced PAK1 activation. Low concentrations of LY294002, a potent inhibitor of phosphoinositide 3-kinase, has been withdrawn from 12-HETE-induced PAK1 activation, meaning that PI-3K activation is upstream of 12-HETE-induced PAK1 activation. Transfection of dominant negative PAK1 inhibited 12-HETE-induced PAK1, cJun N-terminal kinase and extracellular-controlled kinase production in these cells, suggested that PAK1 is upstream activator of 12-HETE-induced JNK1 and ERK1 production in these cells.
Source link: https://doi.org/10.1042/bj3490481
Bovine aortic endothelial and smooth-muscle cells down-regulate the rate of glucose transport in the face of hyperglycaemia, ensuring protection against deleterious effects of elevated intracellular glucose levels. When exposed to high glucose levels, these cells reduced the mRNA and protein content of their common glucose transporter, GLUT-1, as well as its plasma membrane content. Inhibition of the lipoxygenase pathway, especially 12-LO, halted this glucose-induced down-regulation process and returned the rate of hexose transport to levels that were seen in vascular cells exposed to normal glucose levels. The vascular cells' concentrations of cell-associated and secreted 12-hydroxyeicosatetraenoic acid, a component of 12-LO, soared by 2–3-fold. In vascular endothelial and smooth-muscle cells, these results show that hyperglycaemia raises the growth rate of 12-HETE, which in turn mediates the down-regulation of GLUT-1 expression and the glucose transport system.
Source link: https://doi.org/10.1042/bj3620413
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