The function of ALOX12 is further clouded by human ALOX15 which metabolizes arachidonic acid primarily to 15(S)-HpETE but also makes lesser but still significant amounts of 12(S)-HpETE (see ALOX15). (wikipedia.org)
12(S)-HETE is the stereospecific hydroxy product from the reduction of 12(S)-hydroperoxy tetraenoic eicosatetraenoic acid [12(S)-HpETE], which itself is a 12-lipoxygenase metabolite of arachidonic acid. (enzolifesciences.com)
15-hydroxyeicosatetraenoic acid [15(S)-HETE] is the major hydroxy derivative of arachidonic acid when acted upon by 15-lipoxygenase. (enzolifesciences.com)
ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a lipoxygenase-type enzyme that in humans is encoded by the ALOX12 gene which is located along with other lipoyxgenases on chromosome 17p13.3. (wikipedia.org)
Metabolites2
Furthermore, di-GA inhibited the generation of lymphendothelial gaps by cancer cell spheroid-secreted lipoxygenase metabolites. (nature.com)
Nevertheless, quercetin is completely converted into its conjugated metabolites by phase-II enzymes during intestinal absorption. (rsc.org)
Cyclooxygenases3
Changes in dietary fatty acids, specifically the polyunsaturated fatty acids of the ω-3 and ω-6 families and some derived eicosanoids from lipoxygenases, cyclooxygenases, and cytochrome P-450, seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. (springer.com)
This includes lipoxygenases, which incorporate one molecule of O2 into the carbon framework and cyclooxygenases, which incorporate two molecules of O2. (vanderbilt.edu)
We have conducted extensive functional studies with lipoxygenases and cyclooxygenases based on available crystal structures and employing exhaustive site-directed mutagenesis. (vanderbilt.edu)
Cytochrome1
The 5-, 12- and 15-HETE are the main forms but others have been detected (8-, 9-, 11-, 15-, 17-, 18-, 19- and 20-HETE, the 16- to 20-HETE being formed via cytochrome P450). (gerli.com)
The plant C18 fatty acids, linoleic acid and linolenic acid, can be converted by the enzymes a -dioxygenase, 9- or 13-lipoxygenase, giving rise to a multitude of oxylipins. (gerli.com)
Metabolite1
15-HETE, as the initial 15-LOX metabolite of AA, was first identified in human atherosclerotic plaque using high-performance liquid chromatography [ 13 ]. (biomedcentral.com)
Lipid2
The products of both pathways of oxygenation are substrates for metabolizing enzymes that generate a panoply of lipid mediators. (vanderbilt.edu)
The work on lipid mediators is focused on endocannabinoid oxygenation products of COX-2 and 15-lipoxygenase whereas the work on lipid peroxidation products is focused on malondialdehyde, 4-hydroxynonenal, and structurally related molecules. (vanderbilt.edu)
Oxidative stress1
Therefore, with the aim to summarize the current knowledge on the initiation of the atherosclerotic process, in this paper, we review the early markers of atherosclerosis and we address the main therapeutic targets for preventing atheroma formation at its very initial stages focusing on inflammation, oxidative stress, endothelial dysfunction, and the interaction between platelets and endothelium. (hindawi.com)
Metabolism1
Here, we explore the likely role of 15-lipoxygenase (LO)-1-mediated AA metabolism,15-oxo-ETE, in the early pathogenesis of atherosclerosis. (biomedcentral.com)
ALOX15B2
human ALOX15B makes 15(S)-HpETE but not 12(S)-HpETE and therefore is not regarded as a 12/15-lipoxygenase. (wikipedia.org)
Two types of 15-LOX have been identified in human, including 15-LOX-1 (encoded by ALOX15 gene) and 15-LOX-2(encoded by ALOX15B gene) [ 2 , 3 ]. (biomedcentral.com)
Mice4
ALOX12, often termed plate platelet-type 12-lipoxygenase, is distinguished from leukocyte-type 12-lipoxygenase which is found in mice, rats, cows, and pigs but not humans. (wikipedia.org)
Studies on the role of ALOX12 in pathophysiology using the main models for such functional studies, rats and mice, are complicated because neither species possesses a lipoxygenase that makes a predominance of 12(S)-HETE and therefore is metabolically equivalent to ALOX12. (wikipedia.org)
For example, the functions inferred for Alox12 in mice made deficient in Alox12 using knockout methods may not indicate a similar function for ALOX12 in humans due to differences in these two enzymes' metabolic activities. (wikipedia.org)
In ex vivo study, exposure of arteries from C57 mice and ApoE−/−mice to 15-oxo-ETE led to significantly increased E-selectin expression and monocyte adhesion. (biomedcentral.com)
Oxidation2
15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE. (biomedcentral.com)
12,13 However, its catechol structure ( o -dihydroxyl structure in the B-ring) leads to pro-oxidant properties by generating ROS during its oxidation process, which may result in quinone toxicity. (rsc.org)
Monocytes2
Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. (hindawi.com)
After 15-oxo-ETE treatment, Human umbilical vein endothelial cells (HUVECs) showed more attractive to monocytes, whereas monocyte adhesion is suppressed when treated with PKC inhibitor. (biomedcentral.com)
Acids2
In macrophages, 15-LOX-1 converts AA to 15-hydroperoxyeicosatetraenoic acids (15-HpETEs), which is soon reduced by peroxidase to 15-hydroxyeicosatetraenoic acids (15-HETEs). (biomedcentral.com)
These regio-specific enzymatic reactions between oxygen and polyunsaturated fatty acids formed new compounds, named oxylipins, which are most frequently with the S-configuration (5-HpETE, 12-HpETE or 15-HpETE). (gerli.com)
Pathway1
14,15 Conversely, its pro-oxidant activity may enhance cellular defence against oxidants by stimulating the redox-regulated signal transduction pathway which leads to the gene expression of anti-oxidative enzymes such as heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx). (rsc.org)
Endothelial1
Endothelial dysfunction, as a comprehensive index of the overall CVD risk factor burden includes three main consequences, exposure of adhesion molecules, the activation and aggregation of platelets, cholesterol accumulation [ 20 ]. (biomedcentral.com)
Adhesion2
This is the first report that 15-oxo-ETE promotes early pathological process of atherosclerosis by accelerating E-selectin expression and monocyte adhesion. (biomedcentral.com)
15-oxo-ETE -induced monocyte adhesion is partly attributable to activation of PKC. (biomedcentral.com)
Substrates2
While arachidonate and 12(S)-HETE are the predominant substrates and products, respectively, of ALOX12, the enzyme also metabolizes other PUFA. (wikipedia.org)
To support and extend these in vivo studies, we conduct experiments utilizing adduct-containing duplex DNA molecules or template-primers as substrates for purified DNA polymerases or repair enzymes. (vanderbilt.edu)
Humans1
The HETE are found in many types of cells from invertebrates to humans. (gerli.com)
Serum1
For the quantitative determination of 15(S)-HETE in culture supernatants, plasma, serum, and urine from any species. (enzolifesciences.com)
Species2
It is likely to act as a bioactive compound by exerting reactive oxygen species (ROS)-scavenging activity and/or binding to specific proteins such as oxidative enzymes and transcriptional factors in signal transduction pathways. (rsc.org)
This polyphenolic compound is known to be a strong anti-oxidant which scavenges reactive oxygen species (ROS) directly or effectively inhibits ROS-generating enzymes ( e.g. xanthine oxidase, lipoxygenase). (rsc.org)
Cellular1
3,8-9 In fact, there is a great interest in the understanding of its structure and its mechanism of action, particularly of the molecular pathways involved in its recognition and cellular signaling, 10-15 as well as the forms of its inactivation 3,16 . (bvsalud.org)
Biological1
However, relatively little is known about the biological effects of 15-oxo-ETE in cardiovascular disease. (biomedcentral.com)
Recruitment2
15(S)-HETE acts as a paracrine regulator of smooth muscle and lung neutrophil recruitment, and elevated levels of 15(S)-HETE are associated with asthma, rhinitis, chronic paranasal sinusitis and rheumatoid arthritis. (enzolifesciences.com)
Monocyte recruitment is the initial incident in atherosclerotic plaque formation, the present study was designed to explore the likely effect of 15-oxo-ETE on monocyte recruitment. (biomedcentral.com)
Studies1
A great number of studies reported that 12/15-lipoxygenase (12/15-LO) played an important role in atherosclerosis. (biomedcentral.com)
Increased 15-oxo-ETE level is found in in patients with acute myocardial infarction (AMI). (biomedcentral.com)
Product1
12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (12(R)-HpETE), a product with very different pathophysiological roles than that of 12(S)-HpETE (see ALOX12B). (wikipedia.org)
Role1
However, the evidence for the role of 15-oxoETE in atherosclerosis is unclear. (biomedcentral.com)
Results1
The 15(S)-HETE EIA kit is a colorimetric competitive enzyme immunoassay kit with results overnight + 1 hour. (enzolifesciences.com)
Levels1
Based predominantly on the presence of its mRNA, human ALOX12 is distributed predominantly in blood platelets and leukocytes and at lower levels in the basal layer of the epidermis (particularly in the skin lesions of psoriasis), islets of Langerhans within the pancreas, and certain cancers. (wikipedia.org)
Cells3
it also promotes the malignant behavior of cultured human cancer cells as well as the growth of certain cancers in animal models (see 12-HETE). (wikipedia.org)
12(S)-HETE is chemotactic and chemokinetic for polymorphonuclear leukocytes and vascular smooth muscle cells. (enzolifesciences.com)
Phase II enzymes present in the intestinal epithelial cells and the liver cells facilitate their metabolic conversion to glucuronide and sulfate conjugates. (rsc.org)