ALOX15

Arachidonate 15-lipoxygenase, Oryctolagus cuniculus.
ALOX15
Identifiers
Aliases ALOX15, 12-LOX, 15-LOX-1, 15LOX-1, arachidonate 15-lipoxygenase
External IDs MGI: 87997 HomoloGene: 44935 GeneCards: ALOX15
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

246

11687

Ensembl

ENSG00000161905

ENSMUSG00000018924

UniProt

P16050

P39654

RefSeq (mRNA)

NM_001140

NM_009660

RefSeq (protein)

NP_001131.3

NP_033790.3

Location (UCSC) Chr 17: 4.63 – 4.64 Mb Chr 11: 70.34 – 70.35 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically important products. In humans, it is encoded by the ALOX15 gene located on chromosome 17p13.3.[3] This 11 kilobase pair gene consists of 14 exons and 13 introns coding for a 75 kiloDalton protein composed of 662 amino acids. 15-LO is to be distinguished from another human 15-lipoxygenase enzyme, ALOX15B (also termed 15-lipoxygenase-2).[4] Orthologs of ALOX15, termed Alox15, are widely distributed in animal and plant species but commonly have different enzyme activities and make somewhat different products than ALOX15.

Nomenclature

Human ALOX15 was initially named arachidonate 15-lipoxygenase or 15-lipoxygenase but subsequent studies uncovered a second human enzyme with 15-lipoxygenase activity as well as various non-human mammalian Alox15 enzymes that are closely related to and therefore orthologs of human ALOX15. Many of the latter Alox15 enzymes nonetheless possess predominantly or exclusively 12-lipoxygenase rather than 15-lipoxygenase activity. Consequently, human ALOX15 is now referred to as arachidonate-15-lipoxygenase-1, 15-lipoxygenase-1, 15-LOX-1, 15-LO-1, human 12/15-lipoxygenase, leukocyte-type arachidonate 12-lipoxygenase, or arachidonate omega-6 lipoxygenase. The second discovered human 15-lipoxygenase, a product of the ALOX15B gene, is termed ALOX15B, arachidonate 15-lipoxygenase 2, 15-lipoxygenase-2, 15-LOX-2, 15-LO-2, arachidonate 15-lipoxygenase type II, arachidonate 15-lipoxygenase, second type, and arachidonate 15-lipoxygenase; and mouse, rat, and rabbit rodent orthologs of human ALOX15, which share 74-81% amino acid identity with the human enzyme, are commonly termed Alox15, 12/15-lipoxygenase, 12/15-LOX, or 12/15-LO).[3][4]

Both human ALOX15 and ALOX15B genes are located on chromosome 17; their product proteins have an amino acid sequence identity of only ~38%; they also differ in the polyunsaturated fatty acids that they prefer as substrates and exhibit different product profiles when acting on the same substrates.[4][5]

Tissue distribution

Human ALOX15 protein is highly expressed in circulating blood eosinophils and reticulocytes, cells, bronchial airway epithelial cells, mammary epithelial cells, the Reed-Sternberg cells of Hodgkin's lymphoma, corneal epithelial cells, and dendritic cells; it is less strongly expressed in alveolar macrophages, tissue mast cells, tissue fibroblasts, circulating blood neutrophils, vascular endothelial cells, joint Synovial membrane cells, seminal fluid, prostate epithelium cells, and mammary ductal epithelial cells.[6][7][8][9]

The distribution of Alox15 in sub-human primates and, in particular, rodents differs significantly from that of human ALOX15; this, along with there different principal product formation (e.g. 12-HETE rather than 15-HETE) has made the findings of Alox15 functions in rat, mouse, or rabbit models difficult to extrapolate to the function of ALOX15 in humans.[4]

Enzyme activities

Lipoxygenase acitivity

ALOX15 and Alox15 enzymes are non-heme, iron-containing dioxygenases. They commonly catalyze the attachment of molecular oxygen O
2 as a peroxy residue to polyunsaturated fatty acids (PUFA) that contain two carbon-carbon double bonds that for the human ALOX15 are located between carbons 10 and 9 and 7 and 6 as numbered counting backward from the last or omega (i.e. ω) carbon at the methyl end of the PUFA (these carbons are also termed ω-10 and ω-9 and ω-7 and ω-6). In PUFAs that do not have a third carbon-carbon double bound between their ω-13 and ω-12 carbons, human ALOX15 forms ω-6 peroxy intermediates; in PUFAs that do have this third double bound, human ALOX15 makes the ω-6 peroxy intermediate but also small amounts of the ω-9 peroxy intermediate. Rodent Alox15 enzymes, in contrast, produce almost exclusively ω-9 peroxy intermediates. Concurrently, ALOX15 and rodent Alox15 enzymes rearrange the carbon-carbon double bonds to bring them into the 1S-hydroxy-2E,4Z-diene configuration. ALOX15 and Alox15 enzymes act with a high degree of Stereospecificity to form products that position the hydroperoxy residue in the S stereoisomer configuration.[10]

Lipohydroperoxidase activity

Human ALOX15 can also convert the peroxy PUFA intermediate to a cyclic ether with a three-atom ring, i.e. an epoxide intermediate that is attacked by a water molecule to form epoxy-hydrpoxy PUFA products.[4] Eoxins stimulate vascular permeability in an ex vivo human vascular endothelial model system.[11]

Leukotriene synthase activity

The PUFA epoxide of arachidonic acid made by ALOX15 may also be conjugated with glutathione to form eoxin A4 which product can be further metabolized to eoxin B4, eoxin C4, and eoxin D4.[4]

Substrates, substrate metabolites, and metabolite activities

Among their physiological substrates, human and rodent AlOX15 enzymes act on linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid when presented not only as free acids but also when incorporated as esters in phospholipids, glycerides, or Cholesteryl esters. The human enzyme is particularly active on linoleic acid, preferring it over arachidonic acid' it is less active on PUFA that are esters within the cited lipids.[4]

Arachidonic acid

Arachidonic acid (AA) has double bonds between carbons 5-6, 8-9, 11-12, and 14-15; these double bounds are in the cis (see Cis–trans isomerism or Z as opposed to the trans or E configuration. ALOX15 adds a hyroperoxy residue to AA at carbons 15 and to a lesser extent 12 to from 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE) and 12(S)-hydroperoxy-5Z,8Z,10E, 15S-eicosatetraenoic acid (12(S)-HpETE); the purified enzyme makes 15(S)-HpETE and 12(S)-HpETE in a product ratio of ~4-9 to 1.[12] Both products may be rapidly reduced by ubiquitous cellular Glutathione peroxidase enzymes to their corresponding hydroxy analogs, 15(S)-HETE (see 15-hydroxyicosatetraenoic acid) and 12(S)-HETE (see 12-Hydroxyeicosatetraenoic acid). 15(S)-HpETE and 15(S)-HETE bind to and activate the Leukotriene B4 receptor 2, activate the Peroxisome proliferator-activated receptor gamma, and at high concentrations cause cells to generate toxic reactive oxygen species; one or more of these effects may be at least in part responsible for their ability to promote inflammatory responses, alter the growth of various times of human cancer cell lines, contract various types of blood vessels, and stimulate pathological fibrosis in pulmonary arteries and liver (see 15-Hydroxyicosatetraenoic acid#15(S)-HpETE and 15(S)-HETE). 15(S)-HpETE and 15(S)-HETE are esterified into membrane phospholipids where they may be stored and subsequently released during cell stimulation. As one aspect of this processing, the two products are progressively esterified in mitochondria membrane phospholipids during the maturation of red blood cells (see erythropoiesis) and thereby may serve to signal for the degradation of the mitochondria and the maturation of these precursors to red blood cells in mice. This pathway operates along with two other mitochondria-removing pathways and therefore does not appear essential for mouse red blood cell maturation.[4]

15-(S)-HpETE and 15(S)-HETE may be further metabolized to various bioactive products including:

The minor products of ALOX15, 12-(S)-HpETE and 12(S)-HETE, possess a broad range of activities. One or both of these compounds stimulates cells by binding with and activating two G protein-coupled receptors, GPR31 and the Leukotriene B4 receptor 2; 12S-HETE also acts as a receptor antagonist by binding to but not stimulating the Thromboxane receptor thereby inhibiting the actions of Thromboxane A2 and Prostaglandin H2 (see 12-Hydroxyeicosatetraenoic acid#Receptor targets and mechanisms of action). As at least a partial consequence of these receptor-directed actions, one or both the two ALOX15 products exhibit pro-inflammation, diabetes-inducing, and vasodilation activities in animal models; cancer-promoting activity on cultured human cancer cells; and other actions (see 12-Hydroxyeicosatetraenoic acid#Activities and possible clinical significance). The two products are also further metabolized to various bioactive products including:

Docosahexaenoic acid

Human ALOX15 metabolizes docosahexaenoic acid (DHA) to 17S-Hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HpDHA) and 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HDHA).[14] One or both of these products stimulate human breast and prostate cell lines to proliferate in culture and 17S-HDHA possesses potent specialized proresolving mediator activity (see specialized proresolving mediators#DHA-derived Resolvins).[15][16][17][18] One or both of these products may be further metabolized enzymatically to:

Eicosapentaenoic acid

Human ALOX15 metabolizes eicosapentaenoic acid to 15S-hydroperoxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HpEPA) and 15S-hydroxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HEPA); 15S-HEPA inhibits ALOX5-dependent production of the pro-inflammatory mediator, LTB4, in cells, and may thereby serve an anti-inflammatory function.[19] These products may be further metabolized to:

n-3 Docosaexaenoic acid

Human cells and mouse tissues metabolize n-3 docosapentaenoic acid (i.e., 7Z,10Z,13Z,16Z,19Z-docosapentaenoic acid, see clupanodonic acid) to a series of products that have been classified as specialized proresolvin mediators. Base on the analogy to docosahexaenoic acid metabolism to resolving D's, it is presumed that a 15-lipoxygenase, most likely ALOX15 in humans, contributes to this metabolism. These products, termed n-3 Resolven D's (RvDn-3's), are:

Linoleic acid

Human 15-LOX-1 prefers linoleic acid over arachidonic acid as its primary substrate, oxygenating it at carbon 13 to form 13(S)-hydroperoxy-9Z,11E-octadecaenoic acid (13-HpODE or 13(S)-HpODE) which may then be reduce to the corresponding hydroxy derivative, 13(S)-HODE or 13-HODE (see 13-Hydroxyoctadecadienoic acid). In addition to 13(S)-HpODE, non-human 15-LOX1 orthologs such as mouse 12/15-LOX and soybean 15-LOX metabolize linoleic acid to 9-hydroperoxy-10E, 12Z-octadecaenoic acid (9-HpODE or 9(S)-HpODE), which is rapidly converted to 9(S)-HODE (9-HODE) (see 9-Hydroxyoctadecadienoic acid)).[20][21] 13(S)-HODE acts through Peroxisome proliferator-activated receptors and the TRPV1 and human GPR132 receptors to stimulate a variety of responses related to monocyte maturation, lipid metabolism, and neuron activation (see 13-Hydroxyoctadecadienoic acid##Activities of 13-HODEs; 9(S)-HODE is a marker for diseases involving oxidative stress and may contribute to this disease as well as to pain perception and atherosclerosis (see 9-Hydroxyoctadecadienoic acid##Biological and clinical relevancy of 9-HODEs). The two HODEs can be further metabolized to their ketones, 13-oxo-9Z,11E-octadecaenoic acid and 9-oxo-10E, 12Z-octadecaenoic acid; these ketones have been implicated as biomarkers for and possible contributors to the inflammatory component of atherosclerosis, Alzheimer's disease, Steatohepatitis, and other pathological conditions.[22]

Dihomo-γ-linolenic acid

Human neutrophils, presumably using their ALOX 15, metabolize Dihomo-γ-linolenic acid (8Z,11Z,14Z-eicosatrienoic acid) to 15S-hydroperoxy-8Z,11Z,13E-eicosatrienoic acid and 15S-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15S-HETrE). 15S-HETrE possesses anti-inflammatory activity.[19][23]

Gene manipulation studies

Mice made deficient in their 12/15-lipoxygenase gene (Alox15) exhibit a prolonged inflammatory response along with various other aspects of a pathologically enhanced inflammatory response in experimental models of cornea injury, airway inflammation, and peritonitis. These mice also show an accelerated rate of progression of atherosclerosis whereas mice made to overexpress 12/15-lipoxygenase exhibit a delayed rate of atherosclerosis development. Alox15 overexpressing rabbits exhibited reduced tissue destruction and bone loss in a model of periodontitis. Finally, Control mice, but not 12/15-lipoxygense deficient mice responded to eicospentaenoic acid administration by decreasing the number of lesions in a model of endometriosis.[24] These studies indicate that the suppression of inflammation is a major function of 12/15-lipoxygenase and the Specialized proresolving mediators it produces in rodents; although rodent 12/15-lipoxygenase differs from human ALOX15 in the profile of the PUFA metabolites that it produces as well as various other parameters (e.g. tissue distribution), these genetic studies allow that human ALOX15 and the specialized proresolving mediators it produces may play a similar major anti-inflammatory function in humans.

Clinical significance

Inflammatory diseases

À huge and growing number of studies in animal models suggest that 15-LOX-1 and its lipoxin, resolvin, and protectin metabolites (see Specialized proresolving mediators) to inhibit, limit, and resolve diverse inflammatory diseases including periodontitis, peritonitis, sepsis, and other pathogen-induced inflammatory responses; in eczema, arthritis, asthma, cystic fibrosis, atherosclerosis, and adipose tissue inflammation; in the insulin resistance that occurs in obesity that is associated with diabetes and the metabolic syndrome; and in Alzheimer's disease.[25][26][27][28][29] While these studies have not yet been shown to translate to human diseases, first and second generation synthetic resolvins and lipoxins, which unlike their natural analogs, are relatively resistant to metabolic inactivation, have been made and tested as inflammation inhibitors in animal models.[30] These synthetic analogs may prove to be clinically useful for treating the cited human inflammatory diseases.

By metabolizing the ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into 17-HpDHA, 17-HDHA, and the resolvins and protectins, 15-LOX-1's metabolic action is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, act to ameliorate inflammation, inflammation-related diseases, and certain cancers.[9][25]

Asthma

15-LOX-1 and its 5-oxo-15-hydroxy-ETE and eoxin metabolites have been suggested as potential contributors to, and therefore targets for the future study and treatment of, human allergen-induced asthma, aspirin-induced asthma, and perhaps other allergic diseases.[31][32]

Cancer

In colorectal, breast, and kidney cancers, 15-LOX-1 levels are low or absent compared to the cancers' normal tissue counterparts and/or these levels sharply decline as the cancers progress.[8][25][33] These results, as well as a 15-LOX-1 transgene study on colon cancer in mice[34] suggests but do not prove[35] that 15-LOX-1 is a tumor suppressor.

By metabolizing ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into lipoxins and resolvins, 15-LOX-1 is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, may act to reduce the incidence and/or progression of certain cancers.[25] Indeed, the ability of docosahexaenoic acid to inhibit the growth of cultured human prostate cancer cells is totally dependent upon the expression of 15-LOX-1 by these cells and appears due to this enzyme's production of docosahexaenoic acid metabolites such as 17(S)-HpETE, 17(S)-HETE, and/or and, possibly, an isomer of protectin DX (10S, 17S-dihydroxy-4Z, 7Z, 11E, 13Z, 15E, 19Z-docosahexaenoic acid)[9][36]

See also

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 Funk CD, Funk LB, FitzGerald GA, Samuelsson B (May 1992). "Characterization of human 12-lipoxygenase genes". Proceedings of the National Academy of Sciences of the United States of America. 89 (9): 3962–6. doi:10.1073/pnas.89.9.3962. PMC 525611Freely accessible. PMID 1570320.
  4. 1 2 3 4 5 6 7 8 Ivanov I, Kuhn H, Heydeck D (November 2015). "Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15)". Gene. 573 (1): 1–32. doi:10.1016/j.gene.2015.07.073. PMID 26216303.
  5. ↑ Brash AR, Boeglin WE, Chang MS (June 1997). "Discovery of a second 15S-lipoxygenase in humans". Proceedings of the National Academy of Sciences of the United States of America. 94 (12): 6148–52. doi:10.1073/pnas.94.12.6148. PMC 21017Freely accessible. PMID 9177185.
  6. ↑ Claesson HE (September 2009). "On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation and Hodgkin lymphoma". Prostaglandins & Other Lipid Mediators. 89 (3-4): 120–5. doi:10.1016/j.prostaglandins.2008.12.003. PMID 19130894.
  7. ↑ Jiang WG, Watkins G, Douglas-Jones A, Mansel RE (April 2006). "Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 74 (4): 235–45. doi:10.1016/j.plefa.2006.01.009. PMID 16556493.
  8. 1 2 Shureiqi I, Wu Y, Chen D, Yang XL, Guan B, Morris JS, Yang P, Newman RA, Broaddus R, Hamilton SR, Lynch P, Levin B, Fischer SM, Lippman SM (December 2005). "The critical role of 15-lipoxygenase-1 in colorectal epithelial cell terminal differentiation and tumorigenesis". Cancer Research. 65 (24): 11486–92. doi:10.1158/0008-5472.can-05-2180. PMC 1564070Freely accessible. PMID 16357157.
  9. 1 2 3 Hu Y, Sun H, O'Flaherty JT, Edwards IJ (January 2013). "15-Lipoxygenase-1-mediated metabolism of docosahexaenoic acid is required for syndecan-1 signaling and apoptosis in prostate cancer cells". Carcinogenesis. 34 (1): 176–82. doi:10.1093/carcin/bgs324. PMC 3584949Freely accessible. PMID 23066085.
  10. ↑ Kuhn H, Banthiya S, van Leyen K (April 2015). "Mammalian lipoxygenases and their biological relevance". Biochimica et Biophysica Acta. 1851 (4): 308–30. doi:10.1016/j.bbalip.2014.10.002. PMC 4370320Freely accessible. PMID 25316652.
  11. ↑ Feltenmark S, Gautam N, Brunnström A, Griffiths W, Backman L, Edenius C, Lindbom L, Björkholm M, Claesson HE (2008). "Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells". Proceedings of the National Academy of Sciences of the United States of America. 105 (2): 680–5. doi:10.1073/pnas.0710127105. PMC 2206596Freely accessible. PMID 18184802.
  12. ↑ Bryant RW, Bailey JM, Schewe T, Rapoport SM (June 1982). "Positional specificity of a reticulocyte lipoxygenase. Conversion of arachidonic acid to 15-S-hydroperoxy-eicosatetraenoic acid". The Journal of Biological Chemistry. 257 (11): 6050–5. PMID 6804460.
  13. ↑ Yokomizo, T; Kato, K; Hagiya, H; Izumi, T; Shimizu, T (2001). "Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2". Journal of Biological Chemistry. 276 (15): 12454–9. doi:10.1074/jbc.M011361200. PMID 11278893.
  14. ↑ O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJ (2012). "15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival". PLOS ONE. 7 (9): e45480. doi:10.1371/journal.pone.0045480. PMC 3447860Freely accessible. PMID 23029040.
  15. ↑ Hu Y, Sun H, O'Flaherty JT, Edwards IJ (2013). "15-Lipoxygenase-1-mediated metabolism of docosahexaenoic acid is required for syndecan-1 signaling and apoptosis in prostate cancer cells". Carcinogenesis. 34 (1): 176–82. doi:10.1093/carcin/bgs324. PMC 3584949Freely accessible. PMID 23066085.
  16. ↑ O'Flaherty JT, Wooten RE, Samuel MP, Thomas MJ, Levine EA, Case LD, Akman SA, Edwards IJ (2013). "Fatty acid metabolites in rapidly proliferating breast cancer". PLOS ONE. 8 (5): e63076. doi:10.1371/journal.pone.0063076. PMC 3642080Freely accessible. PMID 23658799.
  17. ↑ Ramon S, Baker SF, Sahler JM, Kim N, Feldsott EA, Serhan CN, Martínez-Sobrido L, Topham DJ, Phipps RP (2014). "The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?". Journal of Immunology (Baltimore, Md. : 1950). 193 (12): 6031–40. doi:10.4049/jimmunol.1302795. PMC 4258475Freely accessible. PMID 25392529.
  18. ↑ Kim N, Ramon S, Thatcher TH, Woeller CF, Sime PJ, Phipps RP (2016). "Specialized proresolving mediators (SPMs) inhibit human B-cell IgE production". European Journal of Immunology. 46 (1): 81–91. doi:10.1002/eji.201545673. PMID 26474728.
  19. 1 2 Ziboh VA, Miller CC, Cho Y (2000). "Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites". The American Journal of Clinical Nutrition. 71 (1 Suppl): 361S–6S. PMID 10617998.
  20. ↑ Rankin SM, Parthasarathy S, Steinberg D (March 1991). "Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages". Journal of Lipid Research. 32 (3): 449–56. PMID 1906087.
  21. ↑ "Proof of the enzymatic formation of 9-hydroperoxy-10-trans, 12-cis-octadecadienoic acid from linoleic acid by soya lipoxygenase". Biochim Biophys Acta. 202 (1): 198–9. Feb 1970. doi:10.1016/0005-2760(70)90235-3.
  22. ↑ Yuan ZX, Rapoport SI, Soldin SJ, Remaley AT, Taha AY, Kellom M, Gu J, Sampson M, Ramsden CE (2013). "Identification and profiling of targeted oxidized linoleic acid metabolites in rat plasma by quadrupole time-of-flight mass spectrometry". Biomedical Chromatography : BMC. 27 (4): 422–32. doi:10.1002/bmc.2809. PMC 3552117Freely accessible. PMID 23037960.
  23. ↑ Chilton-Lopez, Surette ME, Swan DD, Fonteh AN, Johnson MM, Chilton FH (1996). "Metabolism of gammalinolenic acid in human neutrophils". Journal of Immunology (Baltimore, Md. : 1950). 156 (8): 2941–7. PMID 8609415.
  24. ↑ Serhan CN, Chiang N, Dalli J (2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC 4515371Freely accessible. PMID 25857211.
  25. 1 2 3 4 López-Vicario C, Rius B, Alcaraz-Quiles J, García-Alonso V, Lopategi A, Titos E, Clària J (May 2015). "Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases". European Journal of Pharmacology. doi:10.1016/j.ejphar.2015.03.092. PMID 25987424.
  26. ↑ Romano M, Cianci E, Simiele F, Recchiuti A (August 2015). "Lipoxins and aspirin-triggered lipoxins in resolution of inflammation". European Journal of Pharmacology. 760: 49–63. doi:10.1016/j.ejphar.2015.03.083. PMID 25895638.
  27. ↑ Cole BK, Lieb DC, Dobrian AD, Nadler JL (Jul 2013). "12- and 15-lipoxygenases in adipose tissue inflammation". Prostaglandins & Other Lipid Mediators. 104-105: 84–92. doi:10.1016/j.prostaglandins.2012.07.004. PMC 3526691Freely accessible. PMID 22951339.
  28. ↑ Russell CD, Schwarze J (February 2014). "The role of pro-resolution lipid mediators in infectious disease". Immunology. 141 (2): 166–73. doi:10.1111/imm.12206. PMC 3904237Freely accessible. PMID 24400794.
  29. ↑ Serhan CN, Chiang N, Dalli J (May 2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC 4515371Freely accessible. PMID 25857211.
  30. ↑ Orr SK, Colas RA, Dalli J, Chiang N, Serhan CN (May 2015). "Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent". American Journal of Physiology. Lung Cellular and Molecular Physiology. 308 (9): L904–11. doi:10.1152/ajplung.00370.2014. PMC 4421783Freely accessible. PMID 25770181.
  31. ↑ James A, Daham K, Backman L, Brunnström A, Tingvall T, Kumlin M, Edenius C, Dahlén SE, Dahlén B, Claesson HE (2013). "The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma". International Archives of Allergy and Immunology. 162 (2): 135–42. doi:10.1159/000351422. PMID 23921438.
  32. ↑ Neighbour H (2014). "Mechanisms of aspirin-intolerant asthma: identifying inflammatory pathways in the pathogenesis of asthma". International Archives of Allergy and Immunology. 163 (1): 1–2. doi:10.1159/000355949. PMID 24247362.
  33. ↑ Gohara A, Eltaki N, Sabry D, Murtagh D, Jankun J, Selman SH, Skrzypczak-Jankun E (October 2012). "Human 5-, 12- and 15-lipoxygenase-1 coexist in kidney but show opposite trends and their balance changes in cancer". Oncology Reports. 28 (4): 1275–82. doi:10.3892/or.2012.1924. PMID 22825379.
  34. ↑ Zuo X, Peng Z, Wu Y, Moussalli MJ, Yang XL, Wang Y, Parker-Thornburg J, Morris JS, Broaddus RR, Fischer SM, Shureiqi I (May 2012). "Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice". Journal of the National Cancer Institute. 104 (9): 709–16. doi:10.1093/jnci/djs187. PMC 3341308Freely accessible. PMID 22472308.
  35. ↑ Umar A (May 2012). "Is 15-LOX-1 a tumor suppressor?". Journal of the National Cancer Institute. 104 (9): 645–7. doi:10.1093/jnci/djs192. PMID 22472307.
  36. ↑ O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJ (2012). "15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival". PloS One. 7 (9): e45480. doi:10.1371/journal.pone.0045480. PMC 3447860Freely accessible. PMID 23029040.

Further reading

  • Kelavkar U, Glasgow W, Eling TE (June 2002). "The effect of 15-lipoxygenase-1 expression on cancer cells". Current Urology Reports. 3 (3): 207–14. doi:10.1007/s11934-002-0066-8. PMID 12084190. 
  • Sigal E, Dicharry S, Highland E, Finkbeiner WE (April 1992). "Cloning of human airway 15-lipoxygenase: identity to the reticulocyte enzyme and expression in epithelium". The American Journal of Physiology. 262 (4 Pt 1): L392–8. PMID 1566855. 
  • Izumi T, Rådmark O, Jörnvall H, Samuelsson B (December 1991). "Purification of two forms of arachidonate 15-lipoxygenase from human leukocytes". European Journal of Biochemistry / FEBS. 202 (3): 1231–8. doi:10.1111/j.1432-1033.1991.tb16495.x. PMID 1662607. 
  • Conrad DJ, Kuhn H, Mulkins M, Highland E, Sigal E (January 1992). "Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase". Proceedings of the National Academy of Sciences of the United States of America. 89 (1): 217–21. doi:10.1073/pnas.89.1.217. PMC 48207Freely accessible. PMID 1729692. 
  • Lei ZM, Rao CV (February 1992). "The expression of 15-lipoxygenase gene and the presence of functional enzyme in cytoplasm and nuclei of pregnancy human myometria". Endocrinology. 130 (2): 861–70. doi:10.1210/en.130.2.861. PMID 1733732. 
  • Izumi T, Rådmark O, Samuelsson B (1991). "Purification of 15-lipoxygenase from human leukocytes, evidence for the presence of isozymes". Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 21A: 101–4. PMID 1825526. 
  • Sloane DL, Leung R, Craik CS, Sigal E (November 1991). "A primary determinant for lipoxygenase positional specificity". Nature. 354 (6349): 149–52. doi:10.1038/354149a0. PMID 1944593. 
  • Nadel JA, Conrad DJ, Ueki IF, Schuster A, Sigal E (April 1991). "Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells". The Journal of Clinical Investigation. 87 (4): 1139–45. doi:10.1172/JCI115110. PMC 295116Freely accessible. PMID 2010530. 
  • Kroschwald P, Kroschwald A, Kühn H, Ludwig P, Thiele BJ, Höhne M, Schewe T, Rapoport SM (April 1989). "Occurrence of the erythroid cell specific arachidonate 15-lipoxygenase in human reticulocytes". Biochemical and Biophysical Research Communications. 160 (2): 954–60. doi:10.1016/0006-291X(89)92528-X. PMID 2719708. 
  • Sigal E, Nadel JA (December 1988). "Arachidonic acid 15-lipoxygenase and airway epithelium. Biologic effects and enzyme purification". The American Review of Respiratory Disease. 138 (6 Pt 2): S35–40. doi:10.1164/ajrccm/138.6_pt_2.s35. PMID 3202520. 
  • Sigal E, Craik CS, Highland E, Grunberger D, Costello LL, Dixon RA, Nadel JA (December 1988). "Molecular cloning and primary structure of human 15-lipoxygenase". Biochemical and Biophysical Research Communications. 157 (2): 457–64. doi:10.1016/S0006-291X(88)80271-7. PMID 3202857. 
  • Sigal E, Grunberger D, Craik CS, Caughey GH, Nadel JA (April 1988). "Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases". The Journal of Biological Chemistry. 263 (11): 5328–32. PMID 3356688. 
  • Nassar GM, Morrow JD, Roberts LJ, Lakkis FG, Badr KF (November 1994). "Induction of 15-lipoxygenase by interleukin-13 in human blood monocytes". The Journal of Biological Chemistry. 269 (44): 27631–4. PMID 7961680. 
  • Kritzik MR, Ziober AF, Dicharry S, Conrad DJ, Sigal E (June 1997). "Characterization and sequence of an additional 15-lipoxygenase transcript and of the human gene". Biochimica et Biophysica Acta. 1352 (3): 267–81. doi:10.1016/s0167-4781(97)00005-5. PMID 9224951. 
  • Brinckmann R, Schnurr K, Heydeck D, Rosenbach T, Kolde G, Kühn H (January 1998). "Membrane translocation of 15-lipoxygenase in hematopoietic cells is calcium-dependent and activates the oxygenase activity of the enzyme". Blood. 91 (1): 64–74. PMID 9414270. 
  • Kelavkar U, Wang S, Montero A, Murtagh J, Shah K, Badr K (July 1998). "Human 15-lipoxygenase gene promoter: analysis and identification of DNA binding sites for IL-13-induced regulatory factors in monocytes". Molecular Biology Reports. 25 (3): 173–82. doi:10.1023/A:1006813009006. PMID 9700053. 
  • Roy B, Cathcart MK (November 1998). "Induction of 15-lipoxygenase expression by IL-13 requires tyrosine phosphorylation of Jak2 and Tyk2 in human monocytes". The Journal of Biological Chemistry. 273 (48): 32023–9. doi:10.1074/jbc.273.48.32023. PMID 9822675. 
  • Kratky D, Lass A, Abuja PM, Esterbauer H, Kühn H (January 1999). "A sensitive chemiluminescence method to measure the lipoxygenase catalyzed oxygenation of complex substrates". Biochimica et Biophysica Acta. 1437 (1): 13–22. doi:10.1016/s0005-2760(98)00176-3. PMID 9931410. 
  • Kelavkar UP, Badr KF (April 1999). "Effects of mutant p53 expression on human 15-lipoxygenase-promoter activity and murine 12/15-lipoxygenase gene expression: evidence that 15-lipoxygenase is a mutator gene". Proceedings of the National Academy of Sciences of the United States of America. 96 (8): 4378–83. doi:10.1073/pnas.96.8.4378. PMC 16340Freely accessible. PMID 10200270. 
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