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  • enzymes
  • The product of this initial metabolic step, 15(S)-hydroperoxyeicosatetraenoic acid, is then converted to a series of eoxins by the same enzymes that metabolize the 5-lipoxygenase product of arachidonic acid metabolism, i.e. 5-hydroperoxy-eicosatetraenoic acid to a series of leukotrienes. (wikipedia.org)
  • Based on detailed analyses of 15-lipoxygenase 1 and stabilized 5-lipoxygenase, lipoxygenase structures consist of a 15 kilodalton N-terminal beta barrel domain, a small (e.g. ~0.6 kilodalton) linker inter-domain (see protein domain#Domains and protein flexibility), and a relatively large C-terminal catalytic domain which contains the non-heme iron critical for the enzymes' catalytic activity. (wikipedia.org)
  • ALOX12B
  • 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)
  • mammals
  • Accordingly, a LOX reacting at the ω-6 position of the substrate (as counted from the tail end of the fatty acid) in plants is referred to as a 13-LOX (alternate: linoleate ω6-LOX) and in mammals as a 15-LOX (alternate: arachidonate ω6-LOX). (glycosciences.de)
  • In mammals a number of lipoxygenases isozymes are involved in the metabolism of eicosanoids (such as prostaglandins, leukotrienes and nonclassic eicosanoids). (wikipedia.org)
  • carbons
  • The PUFA precursors to the eicosanoids include: Arachidonic acid (AA), i.e. 5Z, 8Z,11Z,14Z-eicosatetraenoic acid is ω-6 fatty acid, with four double bonds in the cis configuration (see Cis-trans isomerism) each located between carbons 5-6, 8-9, 11,-12, and 14-15. (wikipedia.org)
  • Dihomo-gamma-linolenic acid (DGLA), 8Z, 11Z,14Z-eicosatrienoic acid is an ω-6 fatty acid with three cis double bonds, each located between carbons 8-9, 11,-12, and 14-15. (wikipedia.org)
  • derivatives
  • Thus, 15(S)-HETE and 15(S)-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives. (wikipedia.org)
  • rabbits
  • In this study, we examined transgenic (TG) rabbits overexpressing 15-LO type I and their response to inflammatory challenge. (jimmunol.org)
  • Skin challenges with either LTB 4 or IL-8 showed that 15-LO TG rabbits give markedly reduced neutrophil (PMN) recruitment and plasma leakage at dermal sites with LTB 4 . (jimmunol.org)
  • Leukocytes from 15-LO TG rabbits gave enhanced LX production, underscoring differences in lipid mediator profiles compared with non-TG rabbits. (jimmunol.org)
  • 15-LO TG rabbits exhibited markedly reduced bone loss and local inflammation. (jimmunol.org)
  • Because enhanced LX production was associated with an increased anti-inflammatory status of 15-LO TG rabbits, a stable analog of 5 S ,6 R ,15 S -trihydroxyeicosa-7 E ,9 E ,11 Z ,13 E -tetraenoic acid (LXA 4 ) was applied to the gingival crevice subject to periodontitis. (jimmunol.org)
  • 10,11 It was also demonstrated that atherosclerotic arteries express increased levels of 15-LOX1 and its AA product, 15-HETE in rabbits. (ahajournals.org)
  • respectively
  • The initial 12(S)-HpETE and 12(R)-HpETE products, regardless of their pathway of formation, are rapidly reduced to 12(S)-HETE and 12(R)-HETE, respectively, by ubiquitous cellular peroxidases, including in particular Glutathione peroxidases or, alternatively, are further metabolized as described below. (wikipedia.org)
  • 15(S)-HETE induced expression and secretion of interleukin-6 (IL-6), as analyzed by RT-PCR and ELISA, respectively. (ahajournals.org)
  • hydroperoxide
  • This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15(S)-HETE. (wikipedia.org)
  • Plant lipoxygenase in conjunction with hydroperoxide lyases are responsible for many fragrances and other signalling compounds. (wikipedia.org)
  • rodent
  • 12-LO was first implicated in diabetes when the increase in 12-Lo expression and 12(S)-hydroxyeicosatetraenoic acid was noted in rodent models of diabetes. (paperity.org)
  • possesses
  • while the third domain of terrestrial life, the archaea, possesses proteins with a slight (~20%) amino acid sequence similarity to lipoxygenases, these proteins lack iron-binding residues and therefore are not projected to possess lipoxygenase activity. (wikipedia.org)
  • pathway
  • Most notably, 5-lipoxygenase (LO) pathway products including LTC 4 and -D 4 , the slow-reacting substances of anaphylaxis, are considered causative agents in airway allergic responses, because they are potent bronchoconstrictors and inducers of leakage permeability changes ( 2 , 3 ). (jimmunol.org)
  • The eoxin-forming pathway sequence is as follows: Arachidonic acid15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HPETE)) via 15-LOX-1 or possibly 15-LOX-2, i.e. (wikipedia.org)
  • allergic
  • Cells and tissues rich in 15-LOX-1 activity such as human eosinophils, umbilical cord-derived mast cells, nasal polyps from allergic subjects, airway epitheleal cells, and L1236 Reed-Sternberg cells derived from Hodgkin's Disease tumors produce eoxins. (wikipedia.org)
  • cells
  • 3) 12-Lipoxygenase of human uterine cervix : Nigam's group of Free University of Berlin had found that human uterine cervix had 12-lipoxygenase activity which was lower in cancer cells. (nii.ac.jp)
  • 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)
  • This duality is typified by signaling cascade that (a) prevents the activation of 5-lipoxygenase (5-LO) in resting cells and (b) results in the formation and release of leukotrienes (LTs), which requires the sequential activation and interaction of at least eight different proteins. (jci.org)
  • Eoxins have been suggested to contribute to inflammation in airway allergies and the development and/or progression of certain types of cancers, particularly Hodgkin's lymphoma (a cancer originating from white blood cells), prostate cancer, and colon carcinoma. (wikipedia.org)
  • lacking 15-LOX-1, it is assumed that these cells employ 12/15-lipoxygenase to initiate this synthesis. (wikipedia.org)
  • 12,13 In addition, recently LOX products of PUFA have also been shown to be potent chemoattractants for residential and invading immune cells recruited to lesion areas. (ahajournals.org)
  • activity
  • Last November Natsuo Ueda visited Free University in Berlin and confirmed the 12-lipoxygenase activity in human uterine cervix. (nii.ac.jp)
  • 15(R)-HpETE and 15(R)-HETE lack some of the activity attributed to their S stereoisomers but can be further to metabolized to bioactive products viz. (wikipedia.org)
  • inflammation
  • These results indicate that overexpression of 15-LO type I and LXA 4 is associated with dampened PMN-mediated tissue degradation and bone loss, suggesting that enhanced anti-inflammation status is an active process. (jimmunol.org)
  • Islet inflammation contributes to beta cell demise in both type 1 and type 2 diabetes. (paperity.org)
  • This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. (paperity.org)
  • chirality
  • In this terminology S refers to the absolute configuration of the chirality of the hydroxy functional group at carbon position 15. (wikipedia.org)
  • hydroperoxy
  • 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15(S)-HpETE): Eoxin A4 Eoxin C4 Eoxin D4 Eoxin E4 A 15-lipoxygenase (i.e. (wikipedia.org)
  • Both stereoisomers are produced from their corresponding S and R 15-HpETE stereoisomers, i.e. 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE) and (15R)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(R)-HpETE). (wikipedia.org)