15-Hydroxyeicosatetraenoic acid

15-Hydroxyeicosatetraenoic acid
Names
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
54845-95-3
3D model (Jmol) Interactive image
ECHA InfoCard 100.214.805
3401
PubChem 5280724
Properties
C20H32O3
Molar mass 320.47 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 endogenous eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types and tissues first produce 15-Hydroperoxyicosatetraenoic acid (15-HpETE). These initial hydroperoxy products are extremely short lived in cells: if not otherwise metabolized, they are reduced to 15-HETE. Both these molecules are hormone-like autocrine and paracrine signalling agents, involved in inflammation response, but often are further metabolized to a wide range of products that are much more potent, including eoxins.[1][2][3]

The production and actions of these molecules and their metabolites often differ greatly depending on cell-type or tissue-type studied. In many ways they are analogous to the more abundant 5-HETE and 5-HPETE.

Nomenclature and Stereoisomers

15-HETE (15(S)-HETE, or 15S-HETE) is unambiguously designated by a shortened version of its IUPAC name, (15S)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid, where S refers to the absolute configuration of the point chirality of the hydroxyl functional group at carbon position 15. Its enantiomer is (15R)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid, i.e. 15(R)-HETE or 15R-HETE. The substance also has Z- and E-stereoisomers (an example of cis–trans isomerism) about each of its double bond moieties at carbon positions 5, 8, 11, and 13.

These stereoisomers are produced from corresponding stereoisomers of 15-HpETE, namely (15S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE), (15R)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(R)-HpETE), and/or a racemic mixture of both stereoisomers. These initial hydroperoxy products are extremely short lived in cells: if not otherwise metabolized, they are reduced to their 15(S)-HETE or 15(R)-HETE analogs.

Both stereoisomers of 15-HETE and probably also of 15-HpETE have signalling activities, as discussed below.

Production

Human tissues attack 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 and 14(S),15(S)-trans-oxido-5Z,8Z,11Z-14,15-leukotriene A4 as minor products; 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic and 12(S)-hydroperoxy-5Z,8Z,10E,15Z-eicosatetraenoic acids, i.e. 12-hydroperoxyicosatetraenoic acid (12-HpETE), are rapidly converted to 15(S)-HETE and 12(S)-hydroxy-5Z,8Z,10E,15Z-eicosatetraenoic acid (12-Hydroxyeicosatetraenoic acid), 12(S)-HETE), respectively, or flow into numerous other metabolic pathways while 14(S),15(S)-trans-oxido-5Z,8Z,11Z-14,15-leukotriene A4 is further 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.[4][5][6][7][8] Human 15-LOX-2 (i.e. ALOX15B) also makes 15(S)-HpETE and 15(S)-HETE but prefers linoleic acid over arachidonic acid as substrate and therefore produces 15(S)-HpETE and 15(S)-HETE as minor products; 15-LO-2 does not make 12-HETE.[8] 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 15(R)-HETE.[9][10] Human prostaglandin-endoperoxide synthase 1 (COX-1) and Prostaglandin-endoperoxide synthase 2 (COX-2) 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] The spontaneous and non-enzymatically-induced autooxidation of arachidonic acid yields 15(R,S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acids[14][15] which in tissues would be rapidly converted to 15(R,S)-HETEs.

Further metabolism of 15(S)-HpETE, 15(S)-HETE, 15(R)-HpETE, 15(R)-HETE, and 15-oxo-ETE

15(S)-HpETE

A) Is rapidly reduced to 15(S)-HETE by ubiquitous cellular peroxidase activities including those of prostaglandin-endoperoxide synthase,[16] prostacyclin synthase, thromboxane synthase,[17] and Glutathione peroxidases.[18]

B) Is acylated into membrane phospholipids, particularly Phosphatidylinositols[19][20] and phosphatidylethanolamine.[21][22] 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[19][20][21][22] thereby forming their 15(S)-HETE-bound phospholipoid analogs. Phosphotidylinositol 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 theirsn-2 positions.[23]

C) Is further 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.[24][25][26] 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.[27] These metabolic transformations are similar to those in the pathway that metabolizes arachidonic acid to [[LTA<sub>4</sub>]], [[LTC<sub>4</sub>]], [[LTD<sub>4</sub>]], and [[LTE<sub>4</sub>]] and presumed to be conducted by the same enzymes [24][26][28] (Eoxins are also termed 14,15-leukotrienes or 14,15-LTs).

D) is also metabolized by 15-LO-1 acid 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]

E) Is further metabolized by 15-LO-1 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]

F) Is 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,8Z12E-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, alternatively, 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]

G) Is 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]

H) Is 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-14S,15S-epoxy-5Z,8Z,11Z-eicosatetraenoic acid) and 15-oxo-ETE).[35]

I) Like other hydroperoxy-containing fatty acids, degrades in cells to various bifuctional potentially toxic electrophiles such as 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal.[36]

J) Is metabolized by cytochrome P450 (CYP) enzymes such as CYP1A1, CYP1A2, CYP1B1, and CYP2S1 to 15-oxo-ETE.[37]

15(S)-HETE

A) Is 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 phosphatidylethanolamaine [21][22] 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.[38]

B) Is acylated into membrane phospholipids, particularly phosphatidylinositol and phosphatidylethanolamine. The phospholipid products contain this 15(S)-HETE most likely at the sn-2 position; these same phospholipids may be made directly by the action of 15-LO-1 on membrane phosphatidylinositols or phosphatidylethanolamines containing arachidonic acid at the sn-2 positions.[39][40][41][42] The phosphatidylethanolamine-bound 15-HETE may be converted to phosphatidylethanolamine-bound 15-oxo-ETE.[22]

C) Is 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).[43][44] or to 5(S),15(S)-dihydroperoxy-6E,8Z,11Z,13E-eicosatetraenoate (i.e., (5(S),15(S)-diHETE).[45][46] 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); these two metabolites may also be made by 15-LO's metabolism of 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid), respectively.[47][48]

15(R)-HpETE

A) This hydroperoxy precursor of 15(R)-HETE made by COX enzymes degrades to 15(R)-HETE.[36] B) Decomposes to various bifuctional potentially toxic electrophiles such as 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal.[36]

15(R)-HETE

A) Like 15(S)-HETE is 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.[38]

B) Is oxygenated by ALOX5 to form its 5,6-oxido derivative which then rearranges to the 15(R) diastereomers of LXA4 and (LXB4 viz., 15-epic 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][49]

15-oxo-ETE

A) Is adducted to glutathione and thereby is preferentially exported from cells through multiple drug resistance transporters MRP1 (see ABCC10 and MRP4 (see ABCC4).[50][51]

Activities of parent metabolites and their metabolites

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 further metabolism to the metabolites sited above.

15(S)-HpETE and 15(S)-HETE bind to the G protein-coupled receptor, Leukotriene B4 receptor 2, i.e. BLT2;[52] this receptor may mediate at least some of their stimulatory activities. Thus, 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,[53] human cancer colon cells,[54] human hepatocellular HepG2 and SMMC7721 cancer cells,[55] mouse 3T3 cells (a fibroblast cell line),[56] rat PA adventitia fibroblasts,[57] Baby hamster kidney cells,[58] and diverse types of vascular endothelial cells.[59][60][61][62] These growth-stimulating effects could contribute to the progression of the cited cancer types in animal models or even humans[53][63] or to the excess fibrosis that occurs, e.g. in the narrowing of pulmonary arteries that contributes to hypoxia-induced pulmonary hypertension,[56] or accompanies liver cirrosis.[64] 15(S)-HETE may also act through BLT2 to stimulate an immediate contractile response in rat pulmonary arteries[65] and the angiogenic effect on human umbilical[60] and dermal[66] endothelial cells of the vasulature.

15(S)-HpETE and 15(S)-HETE also directly bind with and activate peroxisome proliferator-activated receptor gamma.[67] This activation may contribute to the ability of 15(S)-HETE to inhibit the growth of cultured human a) prostate cancer PC-3, LNCaP, and DU145 cells and non-malignant human prostate cells;[68][69] b) lung adenocarcinoma A549 cells;[70] c) human colorectal cancer cells;[71] d) corneal epithelial cells;[72] and e) Jurkat T-cell leukemia cells;[73] The decline in the level of 15(S)-HpETE-forming enzymes and consequential fall in cellular 15-HETE production that occurs in human prostate may be one mechanism by which this and perhaps other human cancers such as those of the colon, rectum, and lung avoid apoptosis and thereby progress and spread.[74][75] In this scenario, 15(S)-HETE and one of its formaing 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.[76][77][78][79][80] 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.[81][82][83]

Several bifuctional 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.[36]

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.[67] 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.[84]

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.[85] 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.[86] 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.[86][87] It is presumed that the preceding activities of 15-oxo-ETE reflect its adduction to the indicated elements.[85] 15-Oxo-ETE, at 2-10 μM, also inhibits the proliferation of cultured Human umbilical vein endothelial cells and LoVo human colorectal cancer cells [88][89] 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.[90] 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.[91]

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).[92] It also binds with and activates PPARγ and thereby can stimulate or inhibit cells independently of OXE1.[93]

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 (see specialized proresolving mediators#lipoxins and Lipoxins).

References

  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. ↑ Schneider, C; Pozzi, A (2011). "Cyclooxygenases and lipoxygenases in cancer". Cancer and Metastasis Reviews. 30 (3–4): 277–94. doi:10.1007/s10555-011-9310-3. PMC 3798028Freely accessible. PMID 22002716.
  3. ↑ Zhu, D; Ran, Y (2012). "Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension". The Journal of Physiological Sciences. 62 (3): 163–72. doi:10.1007/s12576-012-0196-9. PMID 22331435.
  4. ↑ 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): 149–52. doi:10.1016/0014-5793(75)80439-x. PMID 6318.
  5. ↑ J. Biol. Chem 256:9483-9582, 1981
  6. ↑ 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): 14048–53. PMID 6438089.
  7. ↑ 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): L392–8. PMID 1566855.
  8. 1 2 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): 6148–52. Bibcode:1997PNAS...94.6148B. doi:10.1073/pnas.94.12.6148. PMC 21017Freely accessible. PMID 9177185.
  9. ↑ Oliw, E. H. (1993). "Bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases". Biochimica et biophysica acta. 1166 (2–3): 258–63. doi:10.1016/0005-2760(93)90106-j. PMID 8443245.
  10. ↑ 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.
  11. 1 2 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): 575–85. doi:10.1194/jlr.M001719. PMC 2817587Freely accessible. PMID 19752399.
  12. ↑ Serhan, C. N.; Takano, T; Maddox, J. F. (1999). "Aspirin-triggered 15-epi-lipoxin A4 and stable analogs on lipoxin A4 are potent inhibitors of acute inflammation. Receptors and pathways". Advances in experimental medicine and biology. 447: 133–49. PMID 10086190.
  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): 6586–91. doi:10.1074/jbc.275.9.6586. PMID 10692466.
  14. ↑ 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.
  15. ↑ Am. J. Pathol. 104:5-62, 1981
  16. ↑ 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.
  17. ↑ 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): 159–68. doi:10.1016/j.abb.2007.03.012. PMC 2041921Freely accessible. PMID 17459323.
  18. ↑ 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): 407–11. doi:10.1016/0003-9861(92)90704-z. PMID 1314541.
  19. 1 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): 6248–52. doi:10.1073/pnas.87.16.6248. PMC 54510Freely accessible. PMID 2117277.
  20. 1 2 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): 7570–7. PMID 1850411.
  21. 1 2 3 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): 444–50. doi:10.1016/0003-9861(87)90589-3. PMID 3662534.
  22. 1 2 3 4 Hammond, V. J.; Morgan, A. H.; Lauder, S; Thomas, C. P.; Brown, S; Freeman, B. A.; Lloyd, C. M.; Davies, J; Bush, A; Levonen, A. L.; Kansanen, E; Villacorta, L; Chen, Y. E.; Porter, N; Garcia-Diaz, Y. M.; Schopfer, F. J.; O'Donnell, V. B. (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): 41651–66. doi:10.1074/jbc.M112.405407. PMC 3516716Freely accessible. PMID 23060450.
  23. ↑ 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): L457–64. PMID 10484452.
  24. 1 2 Feltenmark, S; Gautam, N; Brunnström, A; Griffiths, W; Backman, L; Edenius, C; Lindbom, L; Björkholm, M; Claesson, H. E. (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): 680–5. Bibcode:2008PNAS..105..680F. doi:10.1073/pnas.0710127105. PMC 2206596Freely accessible. PMID 18184802.
  25. ↑ 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): 120–5. doi:10.1016/j.prostaglandins.2008.12.003. PMID 19130894.
  26. 1 2 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.
  27. ↑ Feltenmark, S; Gautam, N; Brunnström, A; Griffiths, W; Backman, L; Edenius, C; Lindbom, L; Björkholm, M; Claesson, H. E. (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): 680–5. Bibcode:2008PNAS..105..680F. doi:10.1073/pnas.0710127105. PMC 2206596Freely accessible. PMID 18184802.
  28. ↑ Prostaglandins; see Eoxin). 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): 120–5. doi:10.1016/j.prostaglandins.2008.12.003. PMID 19130894.
  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): 976–86. 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): 5523–27. Bibcode:1981PNAS...78.5523M. doi:10.1073/pnas.78.9.5523. PMC 348778Freely accessible. PMID 6272308.
  31. ↑ Kühn, H; Barnett, J; Grunberger, D; Baecker, P; Chow, J; Nguyen, B; Bursztyn-Pettegrew, H; Chan, H; Sigal, E (1993). "Overexpression, purification and characterization of human recombinant 15-lipoxygenase". Biochimica et biophysica acta. 1169 (1): 80–9. doi:10.1016/0005-2760(93)90085-n. PMID 8334154.
  32. 1 2 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. PMC 3471176Freely accessible. 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): H495–507. doi:10.1152/ajpheart.00349.2009. PMC 2724209Freely accessible. 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): 31280–90. doi:10.1074/jbc.M109.025627. PMC 2781526Freely accessible. PMID 19737933.
  35. ↑ Brash, A. R.; Yu, Z; Boeglin, W. E.; Schneider, C (2007). "The hepoxilin connection in the epidermis". FEBS Journal. 274 (14): 3494–502. doi:10.1111/j.1742-4658.2007.05909.x. PMID 17608720.
  36. 1 2 3 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): 28337–46. doi:10.1074/jbc.M504178200. PMID 15964853.
  37. ↑ 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): 180–90. doi:10.1124/dmd.110.035121. PMC 3033693Freely accessible. PMID 21068195.
  38. 1 2 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): 1665–75. doi:10.1021/tx700130p. PMID 17910482.
  39. ↑ 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): 6248–52. doi:10.1073/pnas.87.16.6248. PMC 54510Freely accessible. PMID 2117277.
  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. 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; Coffey, M. J.; Kühn, H; O'Donnell, V. B. (2007). "Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase". Journal of Biological Chemistry. 282 (28): 20151–63. 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.; Collins, P. W.; O'Donnell, V. B. (2010). "Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation". Journal of Biological Chemistry. 285 (10): 6891–903. doi:10.1074/jbc.M109.078428. PMC 2844139Freely accessible. PMID 20061396.
  43. 1 2 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): 141–62. doi:10.1016/j.plefa.2005.05.002. PMID 16005201.
  44. ↑ Buckley, C. D.; Gilroy, D. W.; Serhan, C. N. (2014). "Proresolving lipid mediators and mechanisms in the resolution of acute inflammation". Immunity. 40 (3): 315–27. doi:10.1016/j.immuni.2014.02.009. PMC 4004957Freely accessible. PMID 24656045.
  45. ↑ 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. PMID 6806263.
  46. ↑ 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): 141–62. doi:10.1016/j.plefa.2005.05.002. PMID 16005201.
  47. ↑ 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. 1004 (2): 158–68. doi:10.1016/0005-2760(89)90264-6. PMID 2546590.
  48. ↑ Powell, W. S.; 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.
  49. ↑ Buckley, C. D.; Gilroy, D. W.; Serhan, C. N. (2014). "Proresolving lipid mediators and mechanisms in the resolution of acute inflammation". Immunity. 40 (3): 315–27. doi:10.1016/j.immuni.2014.02.009. PMC 4004957Freely accessible. PMID 24656045.
  50. ↑ 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: 144–53. doi:10.1016/j.cbi.2014.10.029. PMC 4414684Freely accessible. PMID 25450232.
  51. ↑ 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): 3070–7. doi:10.1194/jlr.M040741. PMC 3793611Freely accessible. PMID 23945567.
  52. ↑ 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.
  53. 1 2 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. PMC 3642080Freely accessible. PMID 23658799.
  54. ↑ 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): 1620–8. doi:10.1016/j.biocel.2013.05.009. PMID 23685077.
  55. ↑ Ma, J; Zhang, L; Zhang, J; Liu, M; Wei, L; Shen, T; Ma, C; Wang, Y; Chen, Y; Zhu, D (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): 1031–41. doi:10.1016/j.biocel.2013.02.018. PMID 23474367.
  56. 1 2 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.
  57. ↑ 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): 245–57. doi:10.1002/jcp.24443. PMID 23982954.
  58. ↑ 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. 1167 (1): 102–8. doi:10.1016/0005-2760(93)90223-v. PMID 8384883.
  59. ↑ 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): 7283–91. doi:10.1158/0008-5472.CAN-05-0633. PMID 16103079.
  60. 1 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): 707–18. doi:10.1007/s00011-012-0463-5. PMID 22450700.
  61. ↑ 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.
  62. ↑ 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.
  63. ↑ 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): 1620–8. doi:10.1016/j.biocel.2013.05.009. PMID 23685077.
  64. ↑ Pandey, V; Sultan, M; Kashofer, K; Ralser, M; Amstislavskiy, V; Starmann, J; Osprian, I; Grimm, C; Hache, H; Yaspo, M. L.; Sültmann, H; Trauner, M; Denk, H; Zatloukal, K; Lehrach, H; Wierling, C (2014). "Comparative analysis and modeling of the severity of steatohepatitis in DDC-treated mouse strains". PLoS ONE. 9 (10): e111006. Bibcode:2014PLoSO...9k1006P. doi:10.1371/journal.pone.0111006. PMC 4210132Freely accessible. PMID 25347188.
  65. ↑ Wang, Y; Liang, D; Wang, S; Qiu, Z; Chu, X; Chen, S; Li, L; Nie, X; Zhang, R; Wang, Z; Zhu, D (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): 751–64. doi:10.1093/jb/mvq010. PMID 20139061.
  66. ↑ 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): 7283–91. doi:10.1158/0008-5472.CAN-05-0633. PMID 16103079.
  67. 1 2 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): 171–84. doi:10.1124/mol.109.060541. PMID 19903832.
  68. ↑ Shappell, S. B.; Gupta, R. A.; Manning, S; Whitehead, R; Boeglin, W. E.; Schneider, C; Case, T; Price, J; Jack, G. S.; Wheeler, T. M.; Matusik, R. J.; Brash, A. R.; Dubois, R. N. (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.
  69. ↑ Tang, S; Bhatia, B; Maldonado, C. J.; Yang, P; Newman, R. A.; Liu, J; Chandra, D; Traag, J; Klein, R. D.; Fischer, S. M.; Chopra, D; Shen, J; Zhau, H. E.; Chung, L. W.; Tang, D. G. (2002). "Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells". Journal of Biological Chemistry. 277 (18): 16189–201. doi:10.1074/jbc.M111936200. PMID 11839751.
  70. ↑ 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): 1021–6. PMID 12387716.
  71. ↑ 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): 837–43. doi:10.1002/ijc.11447. PMID 14566836.
  72. ↑ 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): 849–56. doi:10.1167/iovs.04-1166. PMID 15728540.
  73. ↑ 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): 121–33. doi:10.1042/BA20070264. PMID 18494609.
  74. ↑ 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): 235–45. doi:10.1016/S0002-9440(10)65117-6. PMC 1866677Freely accessible. PMID 10393855.
  75. ↑ 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): 135–46. doi:10.1016/j.prostaglandins.2006.05.022. PMID 17164141.
  76. ↑ 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. 1136 (3): 247–52. doi:10.1016/0167-4889(92)90113-p. PMID 1520701.
  77. ↑ 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): 345–50. doi:10.1006/bbrc.2000.2597. PMID 10833416.
  78. ↑ 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): 121–33. doi:10.1042/BA20070264. PMID 18494609.
  79. ↑ 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): 711–5. PMID 19949744.
  80. ↑ Cells. 32:1021-1027, 2011
  81. ↑ 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): 707–18. doi:10.1007/s00011-012-0463-5. PMID 22450700.
  82. ↑ 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. PMC 4207198Freely accessible. PMID 25346880.
  83. ↑ 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): 202–14. doi:10.1016/j.bcp.2007.04.005. PMID 17517376.
  84. ↑ Lee, S. H.; Williams, M. V.; Dubois, R. N.; Blair, I. A. (2005). "Cyclooxygenase-2-mediated DNA damage". Journal of Biological Chemistry. 280 (31): 28337–46. doi:10.1074/jbc.M504178200. PMID 15964853.
  85. 1 2 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: 144–53. doi:10.1016/j.cbi.2014.10.029. PMC 4414684Freely accessible. PMID 25450232.
  86. 1 2 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): 4293–7. doi:10.1016/j.bmc.2014.05.025. PMC 4112157Freely accessible. PMID 24924423.
  87. ↑ 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. PMC 4030715Freely accessible. PMID 24161076.
  88. ↑ 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): 516–25. doi:10.1124/mol.109.057489. PMC 2730384Freely accessible. PMID 19535459.
  89. ↑ 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): 3070–7. doi:10.1194/jlr.M040741. PMC 3793611Freely accessible. PMID 23945567.
  90. ↑ O'Flaherty, J. T.; Rogers, L. C.; Paumi, C. M.; Hantgan, R. R.; Thomas, L. R.; Clay, C. E.; High, K; Chen, Y. Q.; Willingham, M. C.; Smitherman, P. K.; Kute, T. E.; Rao, A; Cramer, S. D.; Morrow, C. S. (2005). "5-Oxo-ETE analogs and the proliferation of cancer cells". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1736 (3): 228–36. doi:10.1016/j.bbalip.2005.08.009. PMID 16154383.
  91. ↑ 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 (Baltimore, Md. : 1950). 157 (10): 4664–71. PMID 8906847.
  92. ↑ O'Flaherty, J. T.; Kuroki, M; Nixon, A. B.; Wijkander, J; Yee, E; Lee, S. L.; Smitherman, P. K.; Wykle, R. L.; Daniel, L. W. (1996). "5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes". Journal of immunology (Baltimore, Md. : 1950). 157 (1): 336–42. PMID 8683135.
  93. ↑ O'Flaherty, J. T.; Rogers, L. C.; Paumi, C. M.; Hantgan, R. R.; Thomas, L. R.; Clay, C. E.; High, K; Chen, Y. Q.; Willingham, M. C.; Smitherman, P. K.; Kute, T. E.; Rao, A; Cramer, S. D.; Morrow, C. S. (2005). "5-Oxo-ETE analogs and the proliferation of cancer cells". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1736 (3): 228–36. doi:10.1016/j.bbalip.2005.08.009. PMID 16154383.

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