Arachidonate 5-lipoxygenase: Difference between revisions
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==ALOX5 regulation== |
==ALOX5 regulation== |
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ALOX5 exists primarily in the cytoplasm and nucleoplasm of cells. Upon cell stimulation, ALOX5: '''a)''' becomes phosphorylated on [[serine]] 523, serine 271, and a third serine by [[Mitogen-activated protein kinase]]s, [[S6 kinase]], [[protein kinase A]], [[protein kinase C]], [[Cdc2]], and/or a Ca<sup>2+</sup>/calmodulin-dependent protein kinase; '''b)''' moves to the nuclear membrane; '''c)''' binds with the [[5-lipoxygenase-activating protein]] (FLAP); and '''d)''' becomes active in metabolizing its substrates. These events, along with rises in cytosolic Ca<sup>2+</sup> levels are induced by cell stimulation such as that caused by [[chemotactic factor]]s on leukocytes. Movement of ALOX5 to nuclear membrane, nuclear membrane [[Phosphatidylcholine]], FLAP, ALOX5 phosphorylation on all three serines, and, perhaps, rises in cytosolic Ca<sup>2+</sup> contribute to and/or are required for the activation of ALOX5.<ref name="pmid24313690">{{cite journal | vauthors = Anwar Y, Sabir JS, Qureshi MI, Saini KS | title = 5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical and pharmacological regulation | journal = Current Drug Targets | volume = 15 | issue = 4 | pages = 410–22 | year = 2014 | pmid = 24313690 | doi = 10.2174/1389450114666131209110745| url = }}</ref> |
ALOX5 exists primarily in the cytoplasm and nucleoplasm of cells. Upon cell stimulation, ALOX5: '''a)''' becomes phosphorylated on [[serine]] 523, serine 271, and a third serine by [[Mitogen-activated protein kinase]]s, [[S6 kinase]], [[protein kinase A]], [[protein kinase C]], [[Cdc2]], and/or a Ca<sup>2+</sup>/calmodulin-dependent protein kinase; '''b)''' moves to the nuclear membrane; '''c)''' binds with the [[5-lipoxygenase-activating protein]] (FLAP); and '''d)''' becomes active in metabolizing its substrates. These events, along with rises in cytosolic Ca<sup>2+</sup> levels are induced by cell stimulation such as that caused by [[chemotactic factor]]s on leukocytes. Movement of ALOX5 to nuclear membrane, nuclear membrane [[Phosphatidylcholine]], FLAP, ALOX5 phosphorylation on all three serines, and, perhaps, rises in cytosolic Ca<sup>2+</sup> contribute to and/or are required for the activation of ALOX5.<ref name="pmid24313690">{{cite journal | vauthors = Anwar Y, Sabir JS, Qureshi MI, Saini KS | title = 5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical and pharmacological regulation | journal = Current Drug Targets | volume = 15 | issue = 4 | pages = 410–22 | year = 2014 | pmid = 24313690 | doi = 10.2174/1389450114666131209110745| url = }}</ref> |
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In addition to its activation, ALOX5 must gain access to its [[polyunsaturated fatty acid]] (PUFA) substrates, which commonly are bound in an ester linkage to the ''sn''2 position of membrane phospholipids (see [[phospholipid]]), in order to form biologically active products. This is accomplished by a large family of [[phospholipase A2]] (PLA<sub>2</sub>) enzymes. The cytosolic PLA<sub>2</sub> set (i.e. cPLA<sub>2</sub>s) of PLA<sub>2</sub> enzymes , in particular, mediates many instances of stimulus-induced release of PUFA in inflammatory cells. For example, chemotactic factors stimulate human neutrophils to '''a)''' raise cytosolic Ca<sup>2+</sup> which triggers the α isoform of cPLA<sub>2</sub> (cPLA<sub>2</sub>α) to move from its normal residence in the cytosol to cellular membranes; '''b)''' activate [[mitogen-activated protein kinase]]s which in turn activate cPLA<sub>2</sub>α by phosphorylating it on ser-505 (other cell types may activate this or other cPLA<sub>2</sub> isoforms using other kinases which phosphorylate them on different serine residues); and '''c)''' release PUFA esterified in membrane phospholipids to FLAP-found ALOX5; and '''d)''' form an array of PUFA metabolites.<ref name="pmid9131168">{{cite journal | vauthors = Wykle RL, Wijkander J, Nixon AB, Daniel LW, O'Flaherty JT | title = Activation of 85 kDa PLA2 by eicosanoids in human neutrophils and eosinophils | journal = Advances in Experimental Medicine and Biology | volume = 416 | issue = | pages = 327–31 | year = 1996 | pmid = 9131168 | doi = | url = }}</ref><ref name="pmid18931897">{{cite journal | vauthors = Burke JE, Dennis EA | title = Phospholipase A2 biochemistry | journal = Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy | volume = 23 | issue = 1 | pages = 49–59 | year = 2009 | pmid = 18931897 | pmc = 2823292 | doi = 10.1007/s10557-008-6132-9 | url = }}</ref> |
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== Substrates, products, product activities == |
== Substrates, products, product activities == |
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Revision as of 13:41, 26 July 2016
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | 5-lipoxygenase | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | GeneCards: [1]; OMA:- orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| arachidonate 5-lipoxygenase | |||||||||
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| Identifiers | |||||||||
| EC no. | 1.13.11.34 | ||||||||
| CAS no. | 80619-02-9 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is an enzyme that in humans is encoded by the ALOX5 gene.[1] Arachidonate 5-lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms EFA substates into leukotrienes as well as a wide range of other biologically active products. ALOX5 is a current target for pharmaceutical intervention in a number of diseases.
ALOX5 gene
The ALOX5 gene, which occupies 71.9 kilobase pairs (kb) on chromosome 10, is composed of 14 exons divided by 13 introns encoding the mature 78 kilodalton (kD) ALOX5 protein consisting of 673 amino acids. The gene promoter region of ALOX5 contains 8 GC boxes but lacks TATA boxes or CAT boxes and thus resembles gene promoters of typical housekeeping genes. Five of the 8 GC boxes are arranged in tandem and recognized by the transcription factors Sp1 and Egr-1. A novel Sp1-binding site occurs close to the major transcription start site (position - 65); a GC-rich core region including the Sp1/Egr-1 sites may be critical for basal 5-LO promoter activity.[2]
ALOX5 expression
Cells primarily involved in regulating inflammation, allergy, and other immune responses, e.g. neutrophils, eosinophils, basophils, monocytes, macrophages, mast cells, dendritic cells, and B-lymphocytes express ALOX5. Platelets, T cells, and erythrocytes are ALOX5-negative. In skin, Langerhans cells strongly express ALOX5. Fibroblasts, smooth muscle cells and endothelial cells express low levels of ALOX5.[2][3]Up-regulation of ALOX5 may occur during the maturation of leukocytes and in human neutrophils treated with granulocyte macrophage colony-stimulating factor and then stimulated with physiological agents.
Aberrant expression of LOX5 is seen in various types of human cancer tumors in vivo as well as in various types of human cancer cell lines in vitro; these tumors and cell lines include those of the pancreas, prostate and colon. ALOX5 products, particularly 5-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors.[2]
Studies with cultured human cells have found that there are a large number of ALOX5 mRNA splice variants due to Alternative splicing. The physiological and/or pathological consequences of this slicing has yet to be defined. In one study, however, human brain tumors were shown to express three mRNA splice variants (2.7, 3.1, and 6.4 kb) in addition to the full 8.6lb species; the abundance of the variants correlated with the malignancy of these tumors suggesting that they may play a role in the development of these tumors.[2]
ALOX5 regulation
ALOX5 exists primarily in the cytoplasm and nucleoplasm of cells. Upon cell stimulation, ALOX5: a) becomes phosphorylated on serine 523, serine 271, and a third serine by Mitogen-activated protein kinases, S6 kinase, protein kinase A, protein kinase C, Cdc2, and/or a Ca2+/calmodulin-dependent protein kinase; b) moves to the nuclear membrane; c) binds with the 5-lipoxygenase-activating protein (FLAP); and d) becomes active in metabolizing its substrates. These events, along with rises in cytosolic Ca2+ levels are induced by cell stimulation such as that caused by chemotactic factors on leukocytes. Movement of ALOX5 to nuclear membrane, nuclear membrane Phosphatidylcholine, FLAP, ALOX5 phosphorylation on all three serines, and, perhaps, rises in cytosolic Ca2+ contribute to and/or are required for the activation of ALOX5.[3]
In addition to its activation, ALOX5 must gain access to its polyunsaturated fatty acid (PUFA) substrates, which commonly are bound in an ester linkage to the sn2 position of membrane phospholipids (see phospholipid), in order to form biologically active products. This is accomplished by a large family of phospholipase A2 (PLA2) enzymes. The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes , in particular, mediates many instances of stimulus-induced release of PUFA in inflammatory cells. For example, chemotactic factors stimulate human neutrophils to a) raise cytosolic Ca2+ which triggers the α isoform of cPLA2 (cPLA2α) to move from its normal residence in the cytosol to cellular membranes; b) activate mitogen-activated protein kinases which in turn activate cPLA2α by phosphorylating it on ser-505 (other cell types may activate this or other cPLA2 isoforms using other kinases which phosphorylate them on different serine residues); and c) release PUFA esterified in membrane phospholipids to FLAP-found ALOX5; and d) form an array of PUFA metabolites.[4][5]
Substrates, products, product activities
ALOX5's Polyunsaturated fatty acid substrates, products , and product activities include:
- ALOX5 metabolizes the omega-6 fatty acid, Arachidonic acid (AA), to 5-hydroperoxyeicosatetraenoic acids (5-HpETE) which is then converted to the physiologically and pathologically important products, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid (5-oxo-ETE), and the 4-series leukotrienes (LTB4, LTC4, LTD4, and LTE4). LTB4, 5-HETE, and 5-oxoETE may contribute to the innate immune response as leukocyte chemotactic factors, i.e. they recruit circulating blood neutrophils and monccytes to sites of microbial invasion, tissue injury, and foreign bodies. When produced in excess, however, they contribute to a wide range of pathological inflammatory responses (see 5-HETE and LTB4). 5-Oxo-ETE is a particularly potent chemotactic factor for eosinophils and may thereby contribute to physiological allergic reactions as well as to pathological allergic diseases (see 5-oxo-eicosatetraenoic acid).[6][7] LTC4, LTD4, and LTE4 contribute to allergic airways reactions such as asthma by contracting these airways (see LTC4, LTD4, and LTE4).[3]
- ALOX5 metabolizes the omega-6 fatty acid, Mead acid (i.e. 5Z,8Z,11Z-eicosatrienoic acid), to 3-series analogs viz., 5(S)-hydroxy-6E,8Z,11Z-eicosatrienoic acid (5-HETrE), 5-oxo-6,8,11-eicosatrienoic acid (5-oxo-ETrE), LTA3, and LTC3; since LTA3 inhibits LTA hydrolase, mead acid metabolizing cells produce relatively little LTB3 and are blocked from metabolizing arachidonic acid to LTB4. On the other hand, 5-oxo-ETrE is almost as potent as 5-oxo-ETE as an eosinophil chemotactic factor and may thereby contribute to the development of physiological and pathological allergic responses.[8]
- ALOX5 metabolizes the omega-3 fatty acid, Eicosapentaenoic acid (EPA), to 5-hydroxyeicosatentaenoic acid which is then converted to 5-series products that are analogous to the arachidonic acid products viz., 5-hydroxy-eioxapentaenoic acid (5-HEPE), 5-oxo-eiocosapentaenoic acid (5-oxo-HEPE), and the 5-series leukotrienes, LTB5, LTC5, LTD5, and LTE5. In general, these eicosapentaenoic acid metabolites are less potent in stimulating cells and tissues than their arachidonic acid metabolites.[7][9]
- ALOX5 cooperates with other lipoxygenase, cyclooxygenase, or cytochrome P450 enzymes in serial metabolic pathways to metabolize: a) arachidonic acid into lipoxins (see Specialized pro-resolving mediators#Lipoxins); b) eicosapentaenoic acid to Resolvins of the E series (seeSpecialized pro-resolving mediators#EPA-derived resolvins); c docosahexaenoic acid to resolvins of the D series (seeSpecialized pro-resolving mediators#DHA-derived Resolvins), Protectins/neuroprotectins (see Specialized pro-resolving mediators#DHA-derived protectins/neuroprotectins), and maresins (see Maresins#DHA-derived Maresins); d) n-3 DPA (i.e. 7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid) to n-3 DPA-derived resolvins (see Specialized pro-resolving mediators#DPA-derived resolvins), n-3 DPA-derived protectins/neuroprotectins (see Specialized pro-resolving mediators#n-3 DPA-derived protectins/neuroprotectins), and n-3 DPA-derived maresins (see Specialized pro-resolving mediators#n-3 DPA-derived maresins). All of these metabolites are Specialized pro-resolving mediators (SPMs), i.e. they possess broad anti-inflammatory, tissue healing, tissue regenerating, and other activities.
On the other hand, certain polyunsaturated fatty acids such as DGLA and linoleic acid inhibit 5-LO from metabolizing arachidonic acid.[10]
Function
5-LO catalyzes oxidation of AA at the 5-position to yield 5-HpETE. 5-LO then converts 5-HpETE to leukotriene A4.[11]
As well as being intermediates in the formation of leukotrienes, hydroperoxides are released from lipoxygenase enzymes. These hydroperoxides are rapidly reduced to their corresponding hydroxy- eicosatetraenoates which may then be further metabolize to active products. 5-LO releases 5-HpETE) which can be further metabolized to 5-oxo-ETE, a potent stimulator of cells involved in allergic reactions such as eosinophils and basophils, and a possible mediator of allergic reactions in humans.[7]
Recently, oxidized lipid products of 5-LO have been measured in membranes of neutrophils in the form of esterified-5-HETE phospholipids. These novel products have biological activities including inhibition of neutrophil extracellular traps.[12][13]
Two other lipoxygenases, 12-LO and 15-LO, act at the 12- and 15-positions, metabolizing arachidonic acid 12- and 15-hydroperoxy intermediates which are then further metabolized to bioactive products including 12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyicosatetraenoic acid (15-HETE), lipoxins, and Hepoxilins.[14]
Gene knockout studies
Alox5-deficient mice exhibit a worsened inflammatory component, failure to resolve inflammation-related responses, and decreased survival in experimental models of respiratory syncytial virus disease, Lyme disease, Toxoplasma gondii disease, and corneal injury. These studies indicate that the suppression of inflammation is a major function of Alox5 and, presumably, the anti-inflammatory specialized pro-resolving mediators (SPMs) that they make, at least in certain rodent inflammation-based model systems. Although rodent Alox5 may differ from human ALOX5 in the profile of the PUFA metabolites they make and their tissue distributions, these genetic studies allow that human ALOX5 along with the SPMs that they contribute to making may play a similar major anti-inflammatory function in humans.[15][16]
Clinical significance
5-LO is a target for pharmaceutical intervention in CAD.[17] Some people with variant alleles for 5-LO are at elevated risk for CAD.[18] 5-LO is expressed in brain cells and may participate in neuropathologic processes.[19]
Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined.[20]
Based on the gene knockout studies cited above, ALOX5 may function to reduce and resolve as well as promote diverse inflammation responses.
5-LO inhibitors
As leukotrienes are important causes of pathological symptoms in asthma, 5-LO inhibitors were developed as asthma treatments. The only 5-LO inhibitor currently licensed for human use in asthma is zileuton.
Minocycline, although primarily a tetracycline antibiotic, is also a 5-LO inhibitor.[21] It may therefore be used as a DMARD-medication in mild rheumatoid arthritis and other rheumatic conditions.[22]
Hyperforin, an active constituent of the herb St John's wort, is a highly potent 5-LO inhibitor.[23] Another natural product, indirubin-3'-monoxime, was also described as selective 5-LO inhibitor effective in a range of cell-free and cell-based models.[24] In addition, curcumin, a constituent of turmeric, is a 5-LO inhibitor in vitro.[25]
Activation
5-LO is activated by 5-lipoxygenase activating protein (FLAP).
Interactions
Arachidonate 5-lipoxygenase has been shown to interact with:
References
- ^ Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B (Apr 1989). "Characterization of the human 5-lipoxygenase gene". Proceedings of the National Academy of Sciences of the United States of America. 86 (8): 2587–91. doi:10.1073/pnas.86.8.2587. PMC 286962. PMID 2565035.
- ^ a b c d Ochs MJ, Suess B, Steinhilber D (2014). "5-lipoxygenase mRNA and protein isoforms". Basic & Clinical Pharmacology & Toxicology. 114 (1): 78–82. doi:10.1111/bcpt.12115. PMID 24020397.
- ^ a b c Anwar Y, Sabir JS, Qureshi MI, Saini KS (2014). "5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical and pharmacological regulation". Current Drug Targets. 15 (4): 410–22. doi:10.2174/1389450114666131209110745. PMID 24313690.
- ^ Wykle RL, Wijkander J, Nixon AB, Daniel LW, O'Flaherty JT (1996). "Activation of 85 kDa PLA2 by eicosanoids in human neutrophils and eosinophils". Advances in Experimental Medicine and Biology. 416: 327–31. PMID 9131168.
- ^ Burke JE, Dennis EA (2009). "Phospholipase A2 biochemistry". Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 23 (1): 49–59. doi:10.1007/s10557-008-6132-9. PMC 2823292. PMID 18931897.
- ^ Rådmark O, Werz O, Steinhilber D, Samuelsson B (2015). "5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease". Biochimica Et Biophysica Acta. 1851 (4): 331–9. doi:10.1016/j.bbalip.2014.08.012. PMID 25152163.
- ^ a b c Powell WS, Rokach J (2013). "The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor". Progress in Lipid Research. 52 (4): 651–65. doi:10.1016/j.plipres.2013.09.001. PMID 24056189. Cite error: The named reference "pmid24056189" was defined multiple times with different content (see the help page).
- ^ Powell WS, Rokach J (2015). "Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid". Biochimica Et Biophysica Acta. 1851 (4): 340–55. doi:10.1016/j.bbalip.2014.10.008. PMID 25449650.
- ^ Maaløe T, Schmidt EB, Svensson M, Aardestrup IV, Christensen JH (Jul 2011). "The effect of n-3 polyunsaturated fatty acids on leukotriene B₄ and leukotriene B₅ production from stimulated neutrophil granulocytes in patients with chronic kidney disease". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 85 (1): 37–41. doi:10.1016/j.plefa.2011.04.004. PMID 21530211.
- ^ Iversen L, Fogh K, Bojesen G, Kragballe K (Jul 1991). "Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophils in vitro. Evidence of formation of antiinflammatory compounds". Agents and Actions. 33 (3–4): 286–91. doi:10.1007/bf01986575. PMID 1659156.
- ^ Reaction R01595 and R03058 at KEGG Pathway Database.
- ^ Clark SR, Guy CJ, Scurr MJ, Taylor PR, Kift-Morgan AP, Hammond VJ, Thomas CP, Coles B, Roberts GW, Eberl M, Jones SA, Topley N, Kotecha S, O'Donnell VB (Feb 2011). "Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human neutrophils and in human and murine infection". Blood. 117 (6): 2033–43. doi:10.1182/blood-2010-04-278887. PMC 3374621. PMID 21177434.
- ^ Pace-Asciak CR (Apr 2015). "Pathophysiology of the hepoxilins". Biochimica et Biophysica Acta. 1851 (4): 383–96. doi:10.1016/j.bbalip.2014.09.007. PMID 25240838.
- ^ Dorlands Medical Dictionary, entries at arachidonate 5-lipoxygenase and following. Retrieved on 2006-02-07.
- ^ Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMID 25359497.
- ^ 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 4515371. PMID 25857211.
- ^ "5-Lipoxygenase, A New Therapeutic And Diagnostic Target For Heart Disease Management". UCLA Case No. 2001-429 PCT Publication Number: WO 03/035670 A2. Archived from the original on 2006-08-30. Retrieved 2007-11-18.
- ^ Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M (Jan 2004). "Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis". The New England Journal of Medicine. 350 (1): 29–37. doi:10.1056/NEJMoa025079. PMID 14702425.
- ^ Zhang L, Zhang WP, Hu H, Wang ML, Sheng WW, Yao HT, Ding W, Chen Z, Wei EQ (Apr 2006). "Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytoma". Neuropathology. 26 (2): 99–106. doi:10.1111/j.1440-1789.2006.00658.x. PMID 16708542.
- ^ "Entrez Gene: ALOX5 arachidonate 5-lipoxygenase".
- ^ can be used as DMARDS. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z (Oct 2004). "Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation". NeuroReport. 15 (14): 2181–4. doi:10.1097/00001756-200410050-00007. PMID 15371729.
- ^ arthritis.about.com: Minocin - Minocycline - Dosage - Side Effects - Drug Interactions
- ^ Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O (Dec 2002). "Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase". Biochemical Pharmacology. 64 (12): 1767–75. doi:10.1016/s0006-2952(02)01387-4. PMID 12445866.
- ^ Blazevic T, Schaible AM, Weinhäupl K, Schachner D, Nikels F, Weinigel C, Barz D, Atanasov AG, Pergola C, Werz O, Dirsch VM, Heiss EH (Mar 2014). "Indirubin-3'-monoxime exerts a dual mode of inhibition towards leukotriene-mediated vascular smooth muscle cell migration". Cardiovascular Research. 101 (3): 522–32. doi:10.1093/cvr/cvt339. PMC 3928003. PMID 24368834.
- ^ Bishayee K, Khuda-Bukhsh AR (Sep 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy". Acta Biochimica et Biophysica Sinica. 45 (9): 709–19. doi:10.1093/abbs/gmt064. PMID 23752617.
- ^ Provost P, Doucet J, Hammarberg T, Gerisch G, Samuelsson B, Radmark O (2001). "5-Lipoxygenase interacts with coactosin-like protein". J. Biol. Chem. 276 (19): 16520–7. doi:10.1074/jbc.M011205200. PMID 11297527.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ VanderNoot VA, Fitzpatrick FA (1995). "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2". Anal. Biochem. 230 (1): 108–14. doi:10.1006/abio.1995.1444. PMID 8585605.
- ^ Lepley RA, Fitzpatrick FA (1994). "5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins". J. Biol. Chem. 269 (39): 24163–8. PMID 7929073.
Further reading
- Rådmark OP (2000). "The molecular biology and regulation of 5-lipoxygenase". Am. J. Respir. Crit. Care Med. 161 (2 Pt 2): S11–5. doi:10.1164/ajrccm.161.supplement_1.ltta-3. PMID 10673219.
- Hammarberg T, Reddy KV, Persson B, Rådmark O (2002). "Calcium binding to 5-lipoxygenase". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 507: 117–21. doi:10.1007/978-1-4615-0193-0_19. ISBN 978-0-306-47283-1. PMID 12664574.
- Ishii S, Noguchi M, Miyano M, Matsumoto T, Noma M (1992). "Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase". Biochem. Biophys. Res. Commun. 182 (3): 1482–90. doi:10.1016/0006-291X(92)91901-2. PMID 1540191.
- Nguyen T, Falgueyret JP, Abramovitz M, Riendeau D (1991). "Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase". J. Biol. Chem. 266 (32): 22057–62. PMID 1939225.
- Hoshiko S, Rådmark O, Samuelsson B (1990). "Characterization of the human 5-lipoxygenase gene promoter". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9073–7. doi:10.1073/pnas.87.23.9073. PMC 55106. PMID 2251250.
- Matsumoto T, Funk CD, Rådmark O, Höög JO, Jörnvall H, Samuelsson B (1988). "Molecular cloning and amino acid sequence of human 5-lipoxygenase". Proc. Natl. Acad. Sci. U.S.A. 85 (1): 26–30. doi:10.1073/pnas.85.1.26. PMC 279474. PMID 2829172.
- Rouzer CA, Kargman S (1988). "Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187". J. Biol. Chem. 263 (22): 10980–8. PMID 3134355.
- Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA (1988). "Cloning of the cDNA for human 5-lipoxygenase". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 416–20. doi:10.1073/pnas.85.2.416. PMC 279559. PMID 3422434.
- Jakobsson PJ, Shaskin P, Larsson P, Feltenmark S, Odlander B, Aguilar-Santelises M, Jondal M, Biberfeld P, Claesson HE (1995). "Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes". Eur. J. Biochem. 232 (1): 37–46. doi:10.1111/j.1432-1033.1995.tb20778.x. PMID 7556168.
- Janssen-Timmen U, Vickers PJ, Wittig U, Lehmann WD, Stark HJ, Fusenig NE, Rosenbach T, Rådmark O, Samuelsson B, Habenicht AJ (1995). "Expression of 5-lipoxygenase in differentiating human skin keratinocytes". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 6966–70. doi:10.1073/pnas.92.15.6966. PMC 41452. PMID 7624354.
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{{cite journal}}: CS1 maint: unflagged free DOI (link) - Nassar GM, Montero A, Fukunaga M, Badr KF (1997). "Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes". Kidney Int. 51 (5): 1520–8. doi:10.1038/ki.1997.209. PMID 9150468.
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External links
- Arachidonate+5-Lipoxygenase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
ref name="pmid24020397">{{cite journal | vauthors = Ochs MJ, Suess B, Steinhilber D | title = 5-lipoxygenase mRNA and protein isoforms | journal = Basic