Chemistry:15-Hydroxyeicosatetraenoic acid

From HandWiki
15-Hydroxyeicosatetraenoic acid
15(S)-HETE.svg
Names
Preferred IUPAC name
(5Z,8Z,11Z,13E,15S)-15-Hydroxyicosa-5,8,11,13-tetraenoic acid
Other names
15-HETE, 15(S)-HETE, 15(S)-HETE
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C20H32O3
Molar mass 320.473 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15(S)-HETE, and 15S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15(S)-hydroperoxyeicosatetraenoic acid (15(S)-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15(S)-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5(S),15(S)-dihydroxy-eicosatetraenoic acid (5(S),15(S)-diHETE), 5-oxo-15(S)-hydroxyeicosatetraenoic acid (5-oxo-15(S)-HETE), a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15(S)-HETE and 15(S)-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.[1][2]

Some cell types (e.g. platelets) metabolize arachidonic acid to the stereoisomer of 15(S)-HpETE, 15(R)-HpETE. Both stereoisomers may also be formed as result of the metabolism of arachidonic acid by cellular microsomes or as a result of arachidonic acid auto-oxidation. Similar to 15(S)-HpETEs, 15(R)-HpETE may be rapidly reduced to 15(R)-HETE. These R,S stereoisomers differ only in having their hydroxy residue in opposite orientations. While the two R stereoisomers are sometimes referred to as 15-HpETE and 15-HETE, proper usage should identify them as R stereoisomers. 15(R)-HpETE and 15(R)-HETE lack some of the activity attributed to their S stereoisomers but can be further metabolized to bioactive products viz., the 15(R) class of lipoxins (also termed epi-lipoxins).[3]

15(S)-HETE, 15(S)-HpETE, and many of their derivative metabolites are thought to have physiologically important functions. They appear to act as hormone-like autocrine and paracrine signaling agents that are involved in regulating inflammatory and perhaps other responses.[1][2][4] Clinically, drugs that are stable analogs, and therefore mimic the anti-inflammatory actions of the lipoxins and drugs that block the production or actions of the pro-inflammatory eoxins may prove useful for treating acute and chronic inflammatory disorders.[5]

Nomenclature and stereoisomers

15(S)-HETE is unambiguously designated by a shortened version of its IUPAC name viz., 15(S)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid. In this terminology S refers to the absolute configuration of the chirality of the hydroxy functional group at carbon position 15. Its 15(R) enantiomer is designated 15(R)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid. Z and E give the cis–trans isomerism about each double bond at carbon positions 5, 8, 11, and 13 with Z indicating cis and E indicating trans isomerism. 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 15(R)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(R)-HpETE).

Production

Human cells release arachidonic acid (i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid) from its storage site in phospholipids by reactions that involve phospholipase C and/or lipase enzymes. This release is stimulated or enhanced by cell stimulation. The freed arachidonic acid is then converted to 15-hydroperoxy/hydroxy products by one or more of the following five pathways.

15-Lipoxygenase-1: Cells metabolize arachidonic acid with 15-lipoxygenase-1 (i.e., 15-LO-1, ALOX15) to form 15(S)-HpETE as a major product and 12(S)-hydroperoxy-5Z,8Z,10E,15Z-eicosatetraenoic acid (12(S)-HpETE) and 14(S),15(S)-trans-oxido-5Z,8Z,11Z-14,15-leukotriene A4 as minor products; 15(S)-HpETE and 12(S)-HpETE are rapidly converted to 15(S)-HETE and 12(S)-hydroxy-5Z,8Z,10E,15Z-eicosatetraenoic acid (12(S)-hydroxyeicosatetraenoic acid), (i.e. 12(S)-HETE), respectively, or further metabolized through other enzyme pathways; 14(S),15(S)-trans-oxido-5Z,8Z,11Z-14,15-leukotriene A4 is metabolized by 15-LO-1 to various isomers of 8,15(S)-dihydroxy-5S,8S,11Z,13S-eicosatetraenoic acids, e.g. 8,15(S)-LTB4's.[6][7][8][9][10]

15-Lipoxygenase-2: Cells also used 15-lipoxygenase 2 (i.e. 15-LOX-2 or ALOX15B) to make 15(S)-HpETE and 15(S)-HETE. However this enzyme has a preference for metabolizing linoleic acid rather than arachidonic acid. It therefore forms linoleic acid metabolites (e.g. 13-hydoxyperoxy/hydroxy-octadecadienoic and 9-hydroperoxy/hydroxyl-octadecadienoic acids) in greater amounts than 15(S)-HpETE and 15(S)-HETE. 15-LOX-2 also differs from 15-LOX-1 in that it does not make 12(S)-HpETE or the leukotriene A4 isomer cited above.[10]

Cyclooxygenase: Cells can use prostaglandin-endoperoxide synthase 1 (i.e. cyclooxygenenase-1 or COX-1) and prostaglandin-endoperoxide synthase 2 (COX-2) to metabolize arachidonic acid primarily to prostaglandins but also to small amounts of 11(R)-HETE and a racemic mixture of 15-HETEs composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE.[11] When pretreated with aspirin, however, COX-1 is inactive while COX-2 attacks arachidonic acid to produce almost exclusively 15(R)-HETE along with its presumed precursor 15(R)-HpETE.[11][12][13]

Microsome metabolism: Human and rat microsomal cytochrome P450s, e.g. CYP2C19, metabolize arachidonic acid to a racemic mixture of 15-HETEs, i.e., 15(R,S)-HETEs, >90% of which is the 15(R) stereoisomer.[14][15]

Autoxidation: The spontaneous and non-enzymatically induced autoxidation of arachidonic acid yields 15(R,S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acids. This non-enzymatic reaction is promoted in cells undergoing oxidative stress. Cells forming this racemic mixture of 15-hydroperoxy products may convert then to 15(R,S)-HETEs and other products. However, the uncontrolled overproduction of the 15-hydroperoxy products may react with other elements to produce cell injury.[16][17]

Further metabolism

The newly formed products formed by the pathways cited in the previous section are bioactive but may also flow into down-stream pathways to form other metabolites with a different sets of bioactivity. The initially formed 15(S)-HpETE may be further metabolized by its parent cell or pass it to nearby cell by a process termed transcellular metabolism.

15(S)-HpETE may be:

  • Rapidly reduced to 15(S)-HETE by ubiquitous cellular peroxidase reactions including those possessed by prostaglandin-endoperoxide synthase-1 and -2,[18] prostacyclin synthase, thromboxane synthase,[19] and various glutathione peroxidases.[20]
  • Acylated into membrane phospholipids, particularly phosphatidylinositols[21][22] and phosphatidylethanolamine.[23][24] The 15(S)-HpETE is bound primarily at the sn-2 position of these phospholipids (see Phospholipase) and may be reduced to 15(S)-HETE[21][22][23][24] thereby forming their 15(S)-HETE-bound phospholipoid analogs. Phosphatidylinositol phospholipids with 15(S)-HETE in the sn-2 position can be attacked by phospholipase C to form corresponding diglycerides with 15(S)-HETE at their sn-2 positions.[25]
  • Metabolized by 15-LO-1 to its 14,15-trans-epoxide, 14,15-trans-epoxide-oxido-5Z,8Z,10E,13E-eicosatetraenoic acid (i.e., eoxin A4 or EXA4), and thereafter to 14(R)-glutothionyl-15(S)-hydroxy-5Z,8Z,10E,13E-eicosatetraenoic acid (i.e. eoxin C4 or EXC4) by leukotriene C4 synthase.[26][27][28] EXC4 contains glutathione (i.e. γ-L-glutamyl-L-cysteinylglycine) bound in the R configuration to carbon 14. EXC4 is further metabolized by removal of the γ-L-glutamyl residue to form EXD4 which is in turn further metabolized by removal of the glycine residue to form EXE4.[26] These metabolic transformations are similar to those in the pathway that metabolizes arachidonic acid to LTA4, LTC4, LTD4, and LTE4 and presumed to be conducted by the same enzymes [26][28][27] (Eoxins are also termed 14,15-leukotrienes or 14,15-LTs).
  • Metabolized alternatively by 15-LO-1 to various 8,15-diHETEs including the two 8(R) and 8(S) diastereomers of 8,15(S)-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-leukotrienes B4) and to two isomeric erythro-14,15-dihydroxy-5-cis-8,10,12-eicosatetraenoic acids (14,15-leukotrienes B4).[29][30][31]
  • Metabolized by 15-LOX-2 to 11(S)-hydroxy-14(S),15(S)-epoxy-5(Z),8(Z),12(E)-eicosatrienoic acid and 13(R)-hydroxy-14(S),15(S)-epoxy-5(Z),8(Z),11(Z)-eicosatrienoic acid; these two products are novel hepoxilins produced by ALOX15 rather than ALOX12, the enzyme responsible for making the various other hepoxilins in humans.[32] The two novel hepoxilins are termed respectively 14,15-HXA3 and 14,15-HXB3. 14,15-HXA3 can be further metabolized by glutathione transferases to 11(S),15(S)-dihydroxy-14(R)-glutathionyl-(5Z),8(Z),12(E)-eicosatrienoic acid (14,15-HXA3C) which is then further metabolized to 11(S),15(S)-dihydroxy-14(R)-cysteinyl-glycyl-(5Z),8(Z),12(E)-eicosatrienoic acid (14,15-HXA3D).[32]
  • Isomerized to 15(S)-hydroxy-11,12-cis-epoxy-5Z,8Z,13E-eicosatrienoic acid (i.e., 15-H-11,12-EETA) by a hydroperoxide isomerase activity and then to 11,12,15-trihydroxy-5Z,8Z,12E-eicosatrienoic acid (i.e. 11,12,15-THETA) and 11,14,15-trihydroxy-5Z,8Z,12E-eicosatrienoic acid (i.e., 11,14,15-THETA) by a soluble epoxide hydrolase activity or, by acid in a non-enzymatic reaction (the R, S configuration of the hydroxy residues in the latter two metabolites has not been defined).[33]
  • Isomerized to threo and erythro diastereoisomers of 13-hydroxy-14,15-cis-epoxy-5Z,8Z,11Z-eicosatrienoic acid (i.e., 15-H-11,12-EETA) by a hydroperoxide isomerase activity, possibly a cytochrome P450, i.e. CYP2J2.[34]
  • Metabolized by cytochrome P450 (CYP) enzymes such as CYP1A1, CYP1A2, CYP1B1, and CYP2S1 to 15-oxo-ETE.[35]
  • Metabolized in skin epidermis by epidermis-type lipoxygenase 3 (eLOX3, encoded by the ALOXE3 gene) to make two products, hepoxilin A3 (HxA3, i.e., 13R-hydroxy-14(S),15(S)-epoxy-5Z,8Z,11Z-eicosatetraenoic acid) and 15-oxo-ETE).[36]
  • Converted to its 14,15-epoxide derivative, eoxin A4, and further metabolized to eoxin C4, eoxin D4, and eoxin E4 (there is no eoxin B4).[37]
  • Degraded non-enzymatically to various cell-injuring electrophiles such as 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal.[38]

15(S)-HETE may be:

  • Oxidized to its keto analog, 15-oxo-ETE, by the same enzyme that converts prostaglandins of the A, E, and F series to their 15-keto analogs viz., NAD+-dependent 15-hydroxyprostaglandin dehydrogenase; 15-oxo-ETE, similar to 15(S)-HETE, may be acylated into membrane phosphatidylethanolamine[23][24] or, similar to 15(S)-HpETE, conjugated with glutathione to form a 13-cysteinyl-glycyl-glutamine adduct viz., 13-glutatione,15-oxo-5(S),8(Z),11(E)-eicosatrienoic acid; the latter metabolite is attacked by γ-glutamyl-transferase to form 13-cysteinyl-glycine,15-oxo-5(S),8(Z),11(E)-eicosatrienoic acid.[39]
  • Acylated into membrane phospholipids, particularly phosphatidylinositol and phosphatidylethanolamine. Phospholipid products contain this 15(S)-HETE most likely at the sn-2 position. 15(S)-HETE-containing-phospholipids may also be made directly by the action of 15-LO-1 on membrane phosphatidylinositols or phosphatidylethanolamines containing arachidonic acid at the sn-2 positions.[21][40][41][42] The phosphatidylethanolamine-bound 15-HETE may be converted to phosphatidylethanolamine-bound 15-oxo-ETE.[24]
  • Oxygenated by 5-lipoxygenase (ALOX5) to form its 5,6-trans epoxide derivative which may then rearrange to the lipoxins (LX), LXA4 (i.e. 5(S),6(R),15(S)-trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid) and LXB4 (i.e., 5(S),14(R),15(S)-trihydroxy-6E,8Z,10E,12E-eicosatetraenoic acid)[3] or to 5(S),15(S)-dihydroperoxy-6E,8Z,11Z,13E-eicosatetraenoate (i.e., 5(S),15(S)-diHETE).[43][44] 5(S),15(S)-diHETE may then be oxidized to 5-oxo-15(S)-hydroxy-6E,8Z,11Z,13E-eicosatetraenoate (i.e., 5-oxo-15(S)-hydroxy-ETE). The latter two metabolites may also be made by 15-LO's metabolism of 5-hydroxyeicosatetraenoic acid (i.e. 5-HETE) and 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-ETE), respectively.[45][46]

15(R)-HpETE may be:

  • Reduced to 15(R)-HETE by the same pathway that reduces 5(S)-HpETE to 15(S)-HETE.[38]
  • Similar to 15(S)-HpETE, subject to decomposition to form various bifuctional potentially toxic electrophiles such as 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal.[38]

15(R)-HETE may be:

  • Similar to 15(S)-HETE, oxidized by NAD-dependent 5-hydroxyprostaglandin dehydrogenase to form 15-oxo-ETE which product can be converted its 13-cysteinyl-glycyl-glutamyl and then 13-cysteinyl-glycine products as described above for 5(S)-HETE.[39]
  • Similar to 15(S)-HETE, oxygenated by ALOX5 to form its 5,6-oxido derivative which then rearranges to the 15(R) diastereomers of LXA4 and (LXB4 viz., 15-epi-LXA4 5(S),6(R),15(R)-trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid) and 15-epi-LXB4 (i.e., 5(S),14(R),15(S)-trihydroxy-6E,8Z,10E,12E-eicosatetraenoic acid, respectively.[43][3]

Activities

15(S)-HpETE and 15(S)-HETE

Most studies have analyzed the action of 15(S)-HETE but not that of its less stable precursor 15(S)-HpETE. Since this precursor is rapidly converted to 15(S)-HETE in cells, it is likely that the two metabolites share similar activities. In many studies, however, is not clear that these activities reflect their intrinsic action or reflect their conversion to the metabolites sited above.

15(S)-HpETE and 15(S)-HETE bind to and activate the G protein-coupled receptor, leukotriene B4 receptor 2, i.e. BLT2.[47] This receptor activation may mediate, at least in part, certain cell-stimulating activities of the two metabolites. BLT2 may be responsible in part or whole for mediating the growth-promoting and anti-apoptosis (i.e. anti-cell death) activities of 15(S)-HETE in cultured human breast cancer cells;[48] human cancer colon cells,[49] human hepatocellular HepG2 and SMMC7721 cancer cells;[50] mouse 3T3 cells (a fibroblast cell line);[51] rat PA adventitia fibroblasts;[52] baby hamster kidney cells;[53] and diverse types of vascular endothelial cells.[54][55][56][57] These growth-stimulating effects could contribute to the progression of the cited cancer types in animal models or even humans[48][49] and the excess fibrosis that causes the narrowing of pulmonary arteries in hypoxia-induced pulmonary hypertension[51] or narrowing of portal arteries in the portal hypertension accompanying liver cirrhosis.[58] 15(S)-HETE may also act through BLT2 to stimulate an immediate contractile response in rat pulmonary arteries[59] and its angiogenic effect on human umbilical[55] and dermal[54] vascular endothelial cells.

15(S)-HpETE and 15(S)-HETE also directly bind with and activate peroxisome proliferator-activated receptor gamma.[60] This activation may contribute to the ability of 15(S)-HETE to inhibit the growth of cultured human prostate cancer PC-3, LNCaP, and DU145 cell lines and non-malignant human prostate cells;[61][62] lung adenocarcinoma A549 cells;[63] human colorectal cancer cells;[64] corneal epithelial cells;[65] and Jurkat T-cell leukemia cells.[66] The decline in the level of 15(S)-HpETE-forming enzymes and consequential fall in cellular 15-HETE production that occurs in human prostate cancer cells may be one mechanism by which this and perhaps other human cancer cells (e.g. those of the colon, rectum, and lung) avoid the apoptosis-inducing actions of 15(S)-HpETE and/or 15(S)-HETE and thereby proliferate and spread.[67][68] In this scenario, 15(S)-HETE and one of its forming enzymes, particularly 15-LOX-2, appear to act as tumor suppressors.

Some of the inhibitory effects of 15(S)-HpETE and 15(S)-HETE, particularly when induced by high concentrations (e.g. >1-10 micromolar), may be due to a less specific mechanism: 15(S)-HpETE and to a lesser extent 15(S)-HETE induce the generation of reactive oxygen species. These species trigger cells to activate their death programs, i.e. apoptosis, and/or are openly toxic to the cells.[69][70][66][71][72] 15(S)-HpETE and 15(S)-HETE inhibit angiogenesis and the growth of cultured human chronic myelogenous leukemia K-562 cells by a mechanism that is associated with the production of reactive oxygen species.[55][73][74]

Several bifunctional electrophilic breakdown products of 15(S)-HpETE, e.g. 4-hydroxy-2(E)-nonenal, 4-hydroperoxy-2(E)-nonenal, 4-oxo-2(E)-nonenal, and cis-4,5-epoxy-2(E)-decanal, are mutagens in mammalian cells and thereby may contripute to the development and/or progression of human cancers.[38]

15(R)-HETE

Similar to 15(S)-HpETE and 15(S)-HETE and with similar potency, 15(R)-HETE binds with and activates peroxisome proliferator-activated receptor gamma.[60] The precursor of 15(R)-HETE, 15(R)-HpETE may, similar to 15(S)-HpETE, break down to the mutagenic products 4-hydroxy-2(E)-nonenal, 4-hydroperoxy-2(E)-nonenal, 4-oxo-2(E)-nonenal, and cis-4,5-epoxy-2(E)-decanal and therefore be involved in cancer development and/or progression.[38]

15-Oxo-ETE

In cultured human monocytes of the THP1 cell line, 15-oxo-ETE inactivates IKKβ (also known as IKK2) thereby blocking this cell's NF-κB-mediated pro-inflammatory responses (e.g. lipopolysaccharide-induced production of TNFα, interleukin 6, and IL1B) while concurrently activating anti-oxidant responses upregulated through the anti-oxidant response element (ARE) by forcing cytosolic KEAP1 to release NFE2L2 which then moves to the nucleus, binds ARE, and induces production of, e.g. hemoxygenase-1, NADPH-quinone oxidoreductase, and possibly glutamate-cysteine ligase modifier.[75] By these actions, 15-oxo-ETE may dampen inflammatory and/or oxidative stress responses. In a cell-free system, 15-oxo-ETE is a moderately potent (IC50=1 μM) inhibitor of 12-lipoxygenase but not other human lipoxygenases.[76] This effect could also have anti-inflammatory and anti-oxidative effects by blocking the formation of 12-HETE and hepoxilins. 15-Oxo-ETE is an example of an α,β unsaturated ketone electrophile. These ketones are highly reactive with nucleophiles, adducting to, for example, the cysteines in transcription and transcription-related regulatory factors and enzymes to form their alkylated and thereby often inactivated products.[76][77] It is presumed that the preceding activities of 15-oxo-ETE reflect its adduction to the indicated elements.[75] 15-Oxo-ETE, at 2-10 μM, also inhibits the proliferation of cultured human umbilical vein endothelial cells and LoVo human colorectal cancer cells [78][79] and at the extremely high concentration of 100 μM inhibits the proliferation of cultured MBA-MD-231 and MCF7 breast cancer cells as well as SKOV3 ovarian cancer cells.[80] They may use a similar "protein-adduction" mechanism; if so the target protein(s) for these effects have not been defined or even suggested. This 15-oxo-ETE action may prove to inhibit the remodeling of blood vessels and reduce the growth of the cited cell types and cancers. At sub-micromolar concentrations, 15-oxo-ETE has weak chemotaxis activity for human monocytes and could serve to recruit this white blood cell into inflammatory responses.[81]

5-Oxo-15(S)-hydroxy-ETE

5-Oxo-15(S)-hydroxy-ETE is properly a member of the 5-HETE family of agonists which binds to the oxoeicosanoid receptor 1, a G protein-coupled receptor, to activate its various target cells. As such, it is a potent stimulator of leukocytes, particularly eosinophils, as well as other OXE1-bearing cells including MDA-MB-231, MCF7, and SKOV3 cancer cells (see 5-Hydroxyicosatetraenoic acid and 5-Oxo-eicosatetraenoic acid).[82] It also binds with and activates PPARγ and thereby can stimulate or inhibit cells independently of OXE1.[80]

Lipoxins

LXA4, LXB4, AT-LXA4, and AT-LXB4 are specialized proresolving mediators, i.e. they potently inhibit the progression and contribute to the resolution of diverse inflammatory and allergic reactions.

Eoxins

Eoxin A4, eoxin C4, eoxin D4, and eoxin E4 are analogs of leukotriene A4, C4, leukotriene D4, and E4. Formation of the leukotrienes is initiated by 5-lipoxygenase metabolism of arachidonic acid to form a 5,6-epoxide viz, leukotriene A4; the latter metabolite is then converted to C4, D4, and E4 in succession. Formation of the eoxins is initiated by a 15-lipoxyenase-mediated metabolism of arachiconic acid to a 14,15-epoxide, eoxin A4 followed by its serial conversion to epoxins C4, D4, and E4 using the same pathways and enzymes that metabolize leukotriene A4 to its down-stream products. Preliminary studies have found that the eoxins have pro-inflammatory actions, suggest that they are involved in severe asthma, aspirin-induced asthma attacks, and perhaps other allergic reactions. The production of eoxins by Reed-Sternburg cells has also led to suggestion that they are involve in the lymphoma of Hodgkins disease.[27] Drugs blocking the 15-lipoxygenases may be useful for inhibiting inflammation by reducing the production of the eoxins.[83]

See also

References

  1. ↑ 1.0 1.1 Moreno, J. J. (2009). "New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development". Biochemical Pharmacology 77 (1): 1–10. doi:10.1016/j.bcp.2008.07.033. PMID 18761324. 
  2. ↑ 2.0 2.1 Schneider, C; Pozzi, A (2011). "Cyclooxygenases and lipoxygenases in cancer". Cancer and Metastasis Reviews 30 (3–4): 277–294. doi:10.1007/s10555-011-9310-3. PMID 22002716. 
  3. ↑ 3.0 3.1 3.2 Buckley, C. D.; Gilroy, D. W.; Serhan, C. N. (2014). "Proresolving lipid mediators and mechanisms in the resolution of acute inflammation". Immunity 40 (3): 315–327. doi:10.1016/j.immuni.2014.02.009. PMID 24656045. 
  4. ↑ Zhu, D; Ran, Y (2012). "Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension". The Journal of Physiological Sciences 62 (3): 163–172. doi:10.1007/s12576-012-0196-9. PMID 22331435. 
  5. ↑ "Diagnosis and treatment of pulmonary infections in adult respiratory distress syndrome". New Horizons (Baltimore, Md.) 1 (4): 550–562. 1993. PMID 8087575. 
  6. ↑ Schewe, T; Halangk, W; Hiebsch, C; Rapoport, S. M. (1975). "A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria". FEBS Letters 60 (1): 149–152. doi:10.1016/0014-5793(75)80439-x. PMID 6318. 
  7. ↑ Bernström K, Hammarström S (1981). "Metabolism of leukotriene D by porcine kidney". J Biol Chem 256 (18): 9579–9582. doi:10.1016/S0021-9258(19)68801-0. PMID 6895224. 
  8. ↑ Hopkins, N. K.; Oglesby, T. D.; Bundy, G. L.; Gorman, R. R. (1984). "Biosynthesis and metabolism of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid by human umbilical vein endothelial cells". The Journal of Biological Chemistry 259 (22): 14048–14053. doi:10.1016/S0021-9258(18)89853-2. PMID 6438089. 
  9. ↑ Sigal, E; Dicharry, S; Highland, E; Finkbeiner, W. E. (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–L398. doi:10.1152/ajplung.1992.262.4.L392. PMID 1566855. 
  10. ↑ 10.0 10.1 Brash, A. R.; Boeglin, W. E.; Chang, M. S. (1997). "Discovery of a second 15S-lipoxygenase in humans". Proceedings of the National Academy of Sciences of the United States of America 94 (12): 6148–6152. doi:10.1073/pnas.94.12.6148. PMID 9177185. Bibcode: 1997PNAS...94.6148B. 
  11. ↑ 11.0 11.1 Mulugeta, S; Suzuki, T; Hernandez, N. T.; Griesser, M; Boeglin, W. E.; Schneider, C (2010). "Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2". The Journal of Lipid Research 51 (3): 575–585. doi:10.1194/jlr.M001719. PMID 19752399. 
  12. ↑ Serhan, C. N.; Takano, T; Maddox, J. F. (1999). "Aspirin-Triggered 15-Epi-Lipoxin A4 and Stable Analogs of Lipoxin A4 are Potent Inhibitors of Acute Inflammation: Receptors and Pathways". Lipoxygenases and their Metabolites. Advances in Experimental Medicine and Biology. 447. pp. 133–149. doi:10.1007/978-1-4615-4861-4_13. ISBN 978-0-306-46044-9. 
  13. ↑ Rowlinson, S. W.; Crews, B. C.; Goodwin, D. C.; Schneider, C; Gierse, J. K.; Marnett, L. J. (2000). "Spatial requirements for 15-(R)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not synthesize 15-(R)-hete". The Journal of Biological Chemistry 275 (9): 6586–6591. doi:10.1074/jbc.275.9.6586. PMID 10692466. 
  14. ↑ Oliw, E. H. (1993). "Bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1166 (2–3): 258–263. doi:10.1016/0005-2760(93)90106-j. PMID 8443245. 
  15. ↑ Bylund, J; Kunz, T; Valmsen, K; Oliw, E. H. (1998). "Cytochromes P450 with bisallylic hydroxylation activity on arachidonic and linoleic acids studied with human recombinant enzymes and with human and rat liver microsomes". The Journal of Pharmacology and Experimental Therapeutics 284 (1): 51–60. PMID 9435160. 
  16. ↑ Boeynaems, J. M.; Oates, J. A.; Hubbard, W. C. (1980). "Preparation and characterization of hydroperoxy-eicosatetraenoic acids (HPETEs)". Prostaglandins 19 (1): 87–97. doi:10.1016/0090-6980(80)90156-2. PMID 7384539. https://dipot.ulb.ac.be/dspace/bitstream/2013/50155/4/17ac6ca9-dd31-4fd8-b4eb-c7d568536ea3.txt. 
  17. ↑ "Neutrophil-aggregating activity of monohydroxyeicosatetraenoic acids". Am. J. Pathol. 104 (1): 55–62. 1981. PMID 7258296. 
  18. ↑ Marshall, Paul J.; Kulmacz, Richard J. (1988). "Prostaglandin H synthase: Distinct binding sites for cyclooxygenase and peroxidase substrates". Archives of Biochemistry and Biophysics 266 (1): 162–170. doi:10.1016/0003-9861(88)90246-9. PMID 3140729. 
  19. ↑ Yeh, H. C.; Tsai, A. L.; Wang, L. H. (2007). "Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases". Archives of Biochemistry and Biophysics 461 (2): 159–168. doi:10.1016/j.abb.2007.03.012. PMID 17459323. 
  20. ↑ Ochi, H; Morita, I; Murota, S (1992). "Roles of glutathione and glutathione peroxidase in the protection against endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid". Archives of Biochemistry and Biophysics 294 (2): 407–411. doi:10.1016/0003-9861(92)90704-z. PMID 1314541. 
  21. ↑ 21.0 21.1 21.2 Brezinski, M. E.; Serhan, C. N. (1990). "Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: Agonist-induced deacylation and transformation of stored hydroxyeicosanoids". Proceedings of the National Academy of Sciences of the United States of America 87 (16): 6248–6252. doi:10.1073/pnas.87.16.6248. PMID 2117277. Bibcode: 1990PNAS...87.6248B. 
  22. ↑ 22.0 22.1 Legrand, A. B.; Lawson, J. A.; Meyrick, B. O.; Blair, I. A.; Oates, J. A. (1991). "Substitution of 15-hydroxyeicosatetraenoic acid in the phosphoinositide signaling pathway". The Journal of Biological Chemistry 266 (12): 7570–7577. doi:10.1016/S0021-9258(20)89485-X. PMID 1850411. 
  23. ↑ 23.0 23.1 23.2 Bergholte, J. M.; Soberman, R. J.; Hayes, R; Murphy, R. C.; Okita, R. T. (1987). "Oxidation of 15-hydroxyeicosatetraenoic acid and other hydroxy fatty acids by lung prostaglandin dehydrogenase". Archives of Biochemistry and Biophysics 257 (2): 444–450. doi:10.1016/0003-9861(87)90589-3. PMID 3662534. 
  24. ↑ 24.0 24.1 24.2 24.3 Hammond, V. J.; Morgan, A. H.; Lauder, S; Thomas, C. P.; Brown, S; Freeman, B. A.; Lloyd, C. M.; Davies, J et al. (2012). "Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ". Journal of Biological Chemistry 287 (50): 41651–41666. doi:10.1074/jbc.M112.405407. PMID 23060450. 
  25. ↑ Alpert, S. E.; Walenga, R. W.; Mandal, A; Bourbon, N; Kester, M (1999). "15-HETE-substituted diglycerides selectively regulate PKC isotypes in human tracheal epithelial cells". The American Journal of Physiology 277 (3 Pt 1): L457–L464. doi:10.1152/ajplung.1999.277.3.L457. PMID 10484452. 
  26. ↑ 26.0 26.1 26.2 Feltenmark, S; Gautam, N; Brunnström, A; Griffiths, W; Backman, L; Edenius, C; Lindbom, L; Björkholm, M et al. (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 105 (2): 680–685. doi:10.1073/pnas.0710127105. PMID 18184802. Bibcode: 2008PNAS..105..680F. 
  27. ↑ 27.0 27.1 27.2 Claesson, H. E. (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): 120–125. doi:10.1016/j.prostaglandins.2008.12.003. PMID 19130894. 
  28. ↑ 28.0 28.1 Sachs-Olsen, C; Sanak, M; Lang, A. M.; Gielicz, A; Mowinckel, P; Lødrup Carlsen, K. C.; Carlsen, K. H.; Szczeklik, A (2010). "Eoxins: A new inflammatory pathway in childhood asthma". Journal of Allergy and Clinical Immunology 126 (4): 859–867.e9. doi:10.1016/j.jaci.2010.07.015. PMID 20920774. https://ruj.uj.edu.pl/xmlui/handle/item/156900. 
  29. ↑ Jubiz, W; Rådmark, O; Lindgren, J. A.; Malmsten, C; Samuelsson, B (1981). "Novel leukotrienes: Products formed by initial oxygenation of arachidonic acid at C-15". Biochemical and Biophysical Research Communications 99 (3): 976–986. doi:10.1016/0006-291x(81)91258-4. PMID 7247953. 
  30. ↑ Maas, R. L.; Brash, A. R.; Oates, J. A. (1981). "A second pathway of leukotriene biosynthesis in porcine leukocytes". Proceedings of the National Academy of Sciences of the United States of America 78 (9): 5523–5527. doi:10.1073/pnas.78.9.5523. PMID 6272308. Bibcode: 1981PNAS...78.5523M. 
  31. ↑ Kühn, H; Barnett, J; Grunberger, D; Baecker, P; Chow, J; Nguyen, B; Bursztyn-Pettegrew, H; Chan, H et al. (1993). "Overexpression, purification and characterization of human recombinant 15-lipoxygenase". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1169 (1): 80–89. doi:10.1016/0005-2760(93)90085-n. PMID 8334154. 
  32. ↑ 32.0 32.1 Vogler, S; Zimmermann, N; Leopold, C; De Joncheere, K (2011). "Pharmaceutical policies in European countries in response to the global financial crisis". Southern Med Review 4 (2): 69–79. doi:10.5655/smr.v4i2.1004. PMID 23093885. 
  33. ↑ Chawengsub, Y; Gauthier, K. M.; Campbell, W. B. (2009). "Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone". AJP: Heart and Circulatory Physiology 297 (2): H495–H507. doi:10.1152/ajpheart.00349.2009. PMID 19525377. 
  34. ↑ Chawengsub, Y; Gauthier, K. M.; Nithipatikom, K; Hammock, B. D.; Falck, J. R.; Narsimhaswamy, D; Campbell, W. B. (2009). "Identification of 13-hydroxy-14,15-epoxyeicosatrienoic acid as an acid-stable endothelium-derived hyperpolarizing factor in rabbit arteries". Journal of Biological Chemistry 284 (45): 31280–31290. doi:10.1074/jbc.M109.025627. PMID 19737933. 
  35. ↑ Bui, P; Imaizumi, S; Beedanagari, S. R.; Reddy, S. T.; Hankinson, O (2011). "Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids". Drug Metabolism and Disposition 39 (2): 180–190. doi:10.1124/dmd.110.035121. PMID 21068195. 
  36. ↑ Brash, A. R.; Yu, Z; Boeglin, W. E.; Schneider, C (2007). "The hepoxilin connection in the epidermis". FEBS Journal 274 (14): 3494–3502. doi:10.1111/j.1742-4658.2007.05909.x. PMID 17608720. 
  37. ↑ "The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma". Int. Arch. Allergy Immunol. 162 (2): 135–142. 2013. doi:10.1159/000351422. PMID 23921438. 
  38. ↑ 38.0 38.1 38.2 38.3 38.4 Lee, S. H.; Williams, M. V.; Dubois, R. N.; Blair, I. A. (2005). "Cyclooxygenase-2-mediated DNA damage". Journal of Biological Chemistry 280 (31): 28337–28346. doi:10.1074/jbc.M504178200. PMID 15964853. 
  39. ↑ 39.0 39.1 Lee, S. H.; Rangiah, K; Williams, M. V.; Wehr, A. Y.; Dubois, R. N.; Blair, I. A. (2007). "Cyclooxygenase-2-mediated metabolism of arachidonic acid to 15-oxo-eicosatetraenoic acid by rat intestinal epithelial cells". Chemical Research in Toxicology 20 (11): 1665–1675. doi:10.1021/tx700130p. PMID 17910482. 
  40. ↑ Brinckmann, R; Schnurr, K; Heydeck, D; Rosenbach, T; Kolde, G; Kühn, H (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. doi:10.1182/blood.V91.1.64. PMID 9414270. 
  41. ↑ Maskrey, B. H.; Bermúdez-Fajardo, A; Morgan, A. H.; Stewart-Jones, E; Dioszeghy, V; Taylor, G. W.; Baker, P. R.; Coles, B et al. (2007). "Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase". Journal of Biological Chemistry 282 (28): 20151–20163. doi:10.1074/jbc.M611776200. PMID 17519227. 
  42. ↑ Thomas, C. P.; Morgan, L. T.; Maskrey, B. H.; Murphy, R. C.; Kühn, H; Hazen, S. L.; Goodall, A. H.; Hamali, H. A. et al. (2010). "Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation". Journal of Biological Chemistry 285 (10): 6891–6903. doi:10.1074/jbc.M109.078428. PMID 20061396. 
  43. ↑ 43.0 43.1 Serhan, C. N. (2005). "Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution". Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (3–4): 141–162. doi:10.1016/j.plefa.2005.05.002. PMID 16005201. 
  44. ↑ Maas, R. L.; Turk, J; Oates, J. A.; Brash, A. R. (1982). "Formation of a novel dihydroxy acid from arachidonic acid by lipoxygenase-catalyzed double oxygenation in rat mononuclear cells and human leukocytes". The Journal of Biological Chemistry 257 (12): 7056–67. doi:10.1016/S0021-9258(18)34537-X. PMID 6806263. 
  45. ↑ Serhan, C. N. (1989). "On the relationship between leukotriene and lipoxin production by human neutrophils: Evidence for differential metabolism of 15-HETE and 5-HETE". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1004 (2): 158–168. doi:10.1016/0005-2760(89)90264-6. PMID 2546590. 
  46. ↑ Powell, W. S.; Rokach, J (2013). "The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor". Progress in Lipid Research 52 (4): 651–665. doi:10.1016/j.plipres.2013.09.001. PMID 24056189. 
  47. ↑ 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): 12454–12459. doi:10.1074/jbc.M011361200. PMID 11278893. 
  48. ↑ 48.0 48.1 O'Flaherty, J. T.; Wooten, R. E.; Samuel, M. P.; Thomas, M. J.; Levine, E. A.; Case, L. D.; Akman, S. A.; Edwards, I. J. (2013). "Fatty acid metabolites in rapidly proliferating breast cancer". PLOS ONE 8 (5): e63076. doi:10.1371/journal.pone.0063076. PMID 23658799. Bibcode: 2013PLoSO...863076O. 
  49. ↑ 49.0 49.1 Cabral, M; Martín-Venegas, R; Moreno, J. J. (2013). "Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth". The International Journal of Biochemistry & Cell Biology 45 (8): 1620–1628. doi:10.1016/j.biocel.2013.05.009. PMID 23685077. 
  50. ↑ Ma, J; Zhang, L; Zhang, J; Liu, M; Wei, L; Shen, T; Ma, C; Wang, Y et al. (2013). "15-lipoxygenase-1/15-hydroxyeicosatetraenoic acid promotes hepatocellular cancer cells growth through protein kinase B and heat shock protein 90 complex activation". The International Journal of Biochemistry & Cell Biology 45 (6): 1031–1041. doi:10.1016/j.biocel.2013.02.018. PMID 23474367. 
  51. ↑ 51.0 51.1 Nieves, D; Moreno, J. J. (2006). "Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth". The Journal of Lipid Research 47 (12): 2681–9. doi:10.1194/jlr.M600212-JLR200. PMID 16980726. 
  52. ↑ Zhang, L; Li, Y; Chen, M; Su, X; Yi, D; Lu, P; Zhu, D (2014). "15-LO/15-HETE mediated vascular adventitia fibrosis via p38 MAPK-dependent TGF-β". Journal of Cellular Physiology 229 (2): 245–257. doi:10.1002/jcp.24443. PMID 23982954. 
  53. ↑ Kiran Kumar, Y. V.; Raghunathan, A; Sailesh, S; Prasad, M; Vemuri, M. C.; Reddanna, P (1993). "Differential effects of 15-HPETE and 15-HETE on BHK-21 cell proliferation and macromolecular composition". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1167 (1): 102–108. doi:10.1016/0005-2760(93)90223-v. PMID 8384883. 
  54. ↑ 54.0 54.1 Zhang, B; Cao, H; Rao, G. N. (2005). "15(S)-hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K-Akt-mTOR-S6K1 signaling". Cancer Research 65 (16): 7283–7291. doi:10.1158/0008-5472.CAN-05-0633. PMID 16103079. 
  55. ↑ 55.0 55.1 55.2 Soumya, S. J.; Binu, S; Helen, A; Anil Kumar, K; Reddanna, P; Sudhakaran, P. R. (2012). "Effect of 15-lipoxygenase metabolites on angiogenesis: 15(S)-HPETE is angiostatic and 15(S)-HETE is angiogenic". Inflammation Research 61 (7): 707–718. doi:10.1007/s00011-012-0463-5. PMID 22450700. 
  56. ↑ Soumya, S. J.; Binu, S; Helen, A; Reddanna, P; Sudhakaran, P. R. (2013). "15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway". Biochemistry and Cell Biology 91 (6): 498–505. doi:10.1139/bcb-2013-0037. PMID 24219292. 
  57. ↑ Li, J; Zhang, Y; Liu, Y; Shen, T; Zhang, H; Xing, Y; Zhu, D (2015). "PGC-1α plays a major role in the anti-apoptotic effect of 15-HETE in pulmonary artery endothelial cells". Respiratory Physiology & Neurobiology 205: 84–91. doi:10.1016/j.resp.2014.10.015. PMID 25447678. 
  58. ↑ Pandey, V; Sultan, M; Kashofer, K; Ralser, M; Amstislavskiy, V; Starmann, J; Osprian, I; Grimm, C et al. (2014). "Comparative analysis and modeling of the severity of steatohepatitis in DDC-treated mouse strains". PLOS ONE 9 (10): e111006. doi:10.1371/journal.pone.0111006. PMID 25347188. Bibcode: 2014PLoSO...9k1006P. 
  59. ↑ Wang, Y; Liang, D; Wang, S; Qiu, Z; Chu, X; Chen, S; Li, L; Nie, X et al. (2010). "Role of the G-protein and tyrosine kinase--Rho/ROK pathways in 15-hydroxyeicosatetraenoic acid induced pulmonary vasoconstriction in hypoxic rats". Journal of Biochemistry 147 (5): 751–764. doi:10.1093/jb/mvq010. PMID 20139061. 
  60. ↑ 60.0 60.1 Naruhn, S; Meissner, W; Adhikary, T; Kaddatz, K; Klein, T; Watzer, B; Müller-Brüsselbach, S; Müller, R (2010). "15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor beta/delta agonist". Molecular Pharmacology 77 (2): 171–184. doi:10.1124/mol.109.060541. PMID 19903832. 
  61. ↑ Shappell, S. B.; Gupta, R. A.; Manning, S; Whitehead, R; Boeglin, W. E.; Schneider, C; Case, T; Price, J et al. (2001). "15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells". Cancer Research 61 (2): 497–503. PMID 11212240. 
  62. ↑ Tang, S; Bhatia, B; Maldonado, C. J.; Yang, P; Newman, R. A.; Liu, J; Chandra, D; Traag, J et al. (2002). "Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells". Journal of Biological Chemistry 277 (18): 16189–16201. doi:10.1074/jbc.M111936200. PMID 11839751. 
  63. ↑ Kudryavtsev, I. A.; Golenko, O. D.; Gudkova, M. V.; Myasishcheva, N. V. (2002). "Arachidonic acid metabolism in growth control of A549 human lung adenocarcinoma cells". Biochemistry. Biokhimiia 67 (9): 1021–1026. doi:10.1023/A:1020526119866. PMID 12387716. 
  64. ↑ Chen, G. G.; Xu, H; Lee, J. F.; Subramaniam, M; Leung, K. L.; Wang, S. H.; Chan, U. P.; Spelsberg, T. C. (2003). "15-hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway". International Journal of Cancer 107 (5): 837–843. doi:10.1002/ijc.11447. PMID 14566836. 
  65. ↑ Chang, M. S.; Schneider, C; Roberts, R. L.; Shappell, S. B.; Haselton, F. R.; Boeglin, W. E.; Brash, A. R. (2005). "Detection and subcellular localization of two 15S-lipoxygenases in human cornea". Investigative Ophthalmology & Visual Science 46 (3): 849–856. doi:10.1167/iovs.04-1166. PMID 15728540. 
  66. ↑ 66.0 66.1 Kumar, K. A.; Arunasree, K. M.; Roy, K. R.; Reddy, N. P.; Aparna, A; Reddy, G. V.; Reddanna, P (2009). "Effects of (15S)-hydroperoxyeicosatetraenoic acid and (15S)-hydroxyeicosatetraenoic acid on the acute- lymphoblastic-leukaemia cell line Jurkat: Activation of the Fas-mediated death pathway". Biotechnology and Applied Biochemistry 52 (Pt 2): 121–133. doi:10.1042/BA20070264. PMID 18494609. 
  67. ↑ Shappell, S. B.; Boeglin, W. E.; Olson, S. J.; Kasper, S; Brash, A. R. (1999). "15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma". The American Journal of Pathology 155 (1): 235–245. doi:10.1016/S0002-9440(10)65117-6. PMID 10393855. 
  68. ↑ Tang, D. G.; Bhatia, B; Tang, S; Schneider-Broussard, R (2007). "15-lipoxygenase 2 (15-LOX2) is a functional tumor suppressor that regulates human prostate epithelial cell differentiation, senescence, and growth (size)". Prostaglandins & Other Lipid Mediators 82 (1–4): 135–146. doi:10.1016/j.prostaglandins.2006.05.022. PMID 17164141. 
  69. ↑ Ochi, H; Morita, I; Murota, S (1992). "Mechanism for endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid, an arachidonate lipoxygenase product". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1136 (3): 247–252. doi:10.1016/0167-4889(92)90113-p. PMID 1520701. 
  70. ↑ MacCarrone, M; Ranalli, M; Bellincampi, L; Salucci, M. L.; Sabatini, S; Melino, G; Finazzi-Agrò, A (2000). "Activation of different lipoxygenase isozymes induces apoptosis in human erythroleukemia and neuroblastoma cells". Biochemical and Biophysical Research Communications 272 (2): 345–350. doi:10.1006/bbrc.2000.2597. PMID 10833416. 
  71. ↑ Dymkowska, D; Wojtczak, L (2009). "Arachidonic acid-induced apoptosis in rat hepatoma AS-30D cells is mediated by reactive oxygen species". Acta Biochimica Polonica 56 (4): 711–715. doi:10.18388/abp.2009_2506. PMID 19949744. 
  72. ↑ Cells. 32:1021-1027, 2011
  73. ↑ Soumya, S. J.; Binu, S; Helen, A; Reddanna, P; Sudhakaran, P. R. (2014). "15-LOX metabolites and angiogenesis: Angiostatic effect of 15(S)-HPETE involves induction of apoptosis in adipose endothelial cells". PeerJ 2: e635. doi:10.7717/peerj.635. PMID 25346880. 
  74. ↑ Mahipal, S. V.; Subhashini, J; Reddy, M. C.; Reddy, M. M.; Anilkumar, K; Roy, K. R.; Reddy, G. V.; Reddanna, P (2007). "Effect of 15-lipoxygenase metabolites, 15-(S)-HPETE and 15-(S)-HETE on chronic myelogenous leukemia cell line K-562: Reactive oxygen species (ROS) mediate caspase-dependent apoptosis". Biochemical Pharmacology 74 (2): 202–214. doi:10.1016/j.bcp.2007.04.005. PMID 17517376. 
  75. ↑ 75.0 75.1 Snyder, N. W.; Golin-Bisello, F; Gao, Y; Blair, I. A.; Freeman, B. A.; Wendell, S. G. (2015). "15-Oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways". Chemico-Biological Interactions 234: 144–153. doi:10.1016/j.cbi.2014.10.029. PMID 25450232. 
  76. ↑ 76.0 76.1 Armstrong, M. M.; Diaz, G; Kenyon, V; Holman, T. R. (2014). "Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes". Bioorganic & Medicinal Chemistry 22 (15): 4293–4297. doi:10.1016/j.bmc.2014.05.025. PMID 24924423. 
  77. ↑ Delmastro-Greenwood, M; Freeman, B. A.; Wendell, S. G. (2014). "Redox-dependent anti-inflammatory signaling actions of unsaturated fatty acids". Annual Review of Physiology 76: 79–105. doi:10.1146/annurev-physiol-021113-170341. PMID 24161076. 
  78. ↑ Wei, C; Zhu, P; Shah, S. J.; Blair, I. A. (2009). "15-oxo-Eicosatetraenoic acid, a metabolite of macrophage 15-hydroxyprostaglandin dehydrogenase that inhibits endothelial cell proliferation". Molecular Pharmacology 76 (3): 516–525. doi:10.1124/mol.109.057489. PMID 19535459. 
  79. ↑ Snyder, N. W.; Revello, S. D.; Liu, X; Zhang, S; Blair, I. A. (2013). "Cellular uptake and antiproliferative effects of 11-oxo-eicosatetraenoic acid". The Journal of Lipid Research 54 (11): 3070–3077. doi:10.1194/jlr.M040741. PMID 23945567. 
  80. ↑ 80.0 80.1 O'Flaherty, J. T.; Rogers, L. C.; Paumi, C. M.; Hantgan, R. R.; Thomas, L. R.; Clay, C. E.; High, K; Chen, Y. Q. et al. (2005). "5-Oxo-ETE analogs and the proliferation of cancer cells". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1736 (3): 228–236. doi:10.1016/j.bbalip.2005.08.009. PMID 16154383. 
  81. ↑ Sozzani, S; Zhou, D; Locati, M; Bernasconi, S; Luini, W; Mantovani, A; O'Flaherty, J. T. (1996). "Stimulating properties of 5-oxo-eicosanoids for human monocytes: Synergism with monocyte chemotactic protein-1 and -3". Journal of Immunology 157 (10): 4664–4671. doi:10.4049/jimmunol.157.10.4664. PMID 8906847. 
  82. ↑ O'Flaherty, J. T.; Kuroki, M; Nixon, A. B.; Wijkander, J; Yee, E; Lee, S. L.; Smitherman, P. K.; Wykle, R. L. et al. (1996). "5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes". Journal of Immunology 157 (1): 336–342. doi:10.4049/jimmunol.157.1.336. PMID 8683135. 
  83. ↑ "15-Lipoxygenase inhibitors: a patent review". Expert Opinion on Therapeutic Patents 26 (1): 65–88. 2016. doi:10.1517/13543776.2016.1113259. PMID 26560362. 

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:15-Hydroxyeicosatetraenoic_acid&oldid=3327847"