Oxoeicosanoid receptor 1

Last updated

OXER1
Identifiers
Aliases OXER1 , GPCR, GPR170, TG1019, oxoeicosanoid (OXE) receptor 1, oxoeicosanoid receptor 1
External IDs HomoloGene: 65034; GeneCards: OXER1; OMA:OXER1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

165140

n/a

Ensembl

ENSG00000162881

n/a

UniProt

Q8TDS5

n/a

RefSeq (mRNA)

NM_148962

n/a

RefSeq (protein)

NP_683765

n/a

Location (UCSC) Chr 2: 42.76 – 42.76 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

Oxoeicosanoid receptor 1 (OXER1) also known as G-protein coupled receptor 170 (GPR170) is a protein that in humans is encoded by the OXER1 gene located on human chromosome 2p21; it is the principal receptor for the 5-Hydroxyicosatetraenoic acid family of carboxy fatty acid metabolites derived from arachidonic acid. [3] [4] [5] The receptor has also been termed hGPCR48, HGPCR48, and R527 but OXER1 is now its preferred designation. [6] [7] [8] [9] [10] [4] [11] OXER1 is a G protein-coupled receptor (GPCR) that is structurally related to the hydroxy-carboxylic acid (HCA) family of G protein-coupled receptors whose three members are HCA1 (GPR81), HCA2 (Niacin receptor 1), and HCA3 (Niacin receptor 2); OXER1 has 30.3%, 30.7%, and 30.7% amino acid sequence identity with these GPCRs, respectively. [12] It is also related (30.4% amino acid sequence identity) to the recently defined receptor, GPR31, for the hydroxyl-carboxy fatty acid 12-HETE. [12] [13]

Contents

Species and tissue distribution

Orthologs of OXER1 are found in various mammalian species including opossums and several species of fish; however, mice and rats lack a clear ortholog of OXER1. [14] [15] This represents an important hindrance to studies on the function of OXER1 since these two mammalian species are the most common and easiest models for investigating the in vivo functions of receptors in mammals and by extrapolation humans. Since mouse cells make and respond to members of the 5-HETE family of agonists, [16] it is most likely that mice do have a receptor that substitutes for OXER1 by mediating their responses to this agonist family. Recently, A G protein-couple receptor of the hydroxy carboxylic acid subfamily, Niacin receptor 1, has been proposed to mediate the responses of mouse tissues to 5-oxo-ETE. [17]

OXER1 is highly expressed by human white blood cells, particularly eosinophils and to a lesser extent neutrophils, basophils, and monocytes; by bronchoalveolar macrophages isolated from human bronchoalveolar lavage washings; [15] and by the human H295R adrenocortical cell line. [17] Various types of human cancer cells lines express OXER1; these include those of the prostate, [18] [19] [20] breast, [21] [22] lung, [23] [24] ovaries, [21] [25] colon, [26] and pancreas. [27] [28] OXER1 is also expressed by the human spleen, lung, liver, and kidney tissues. [29] The exact cell types bearing OXER1 in these tissues has not been defined.

A recent study has found that cats express the OXER1 receptor for 5-oxo-ETE, that feline leukocytes, including eosinophils, have been found to synthesize and be very highly responsive to 5-oxo-ETE, and that 5-oxo-ETE is present in the bronchoalveolar lavage fluid from cats with experimentally induced asthma; these findings suggest that the 5-oxo-ETE/OXER1 axis may play an important role in feline asthma, a common condition in this species, and that felines could serve as a useful animal model to investigate the pathophysiological role of 5-oxo-ETE in asthma and other conditions. [30]

Ligands

The OXER1 G protein-coupled receptor resembles the hydroxy carboxylic acid subfamily of G protein-coupled receptors, which besides GPR109A, niacin receptor 1, and niacin receptor 2 may include the recently defined receptor for 12-HETE, GPR31, not only in its amino acid sequence but also in the hydroxy-carboxylic acid nature of its cognate ligands. [31] [32] Naturally occurring ligands for OXER1 are long chain polyunsaturated fatty acids containing either a hydroxyl (i.e. -OH) or oxo (i.e. =O, keto) residue removed by 5 carbons from each of these acid's carboxy residue. [33]

Agonists

OXER1 is known or presumed to bind and thereby be activated by the following endogenous arachidonic acid metabolites; 5-oxo-ETE>5-oxo-15-hydroxy-ETE>5-hydroperoxyicosatetraenoic acid (5-HpETE)>5-HETE>5,20-diHETE. [3] [33] [34] [35] [36] [37] [38] OXER1 is also activated by metabolites of other polyunsaturated fatty acids that therefore may be categorized as members of the 5-oxo-ETE family of agonists; these agonists include 5(S)-oxo-6E,8Z,11Z-eicosatrienoic acid (a 5-LO metabolite of mead acid); 5(S)-hydroxy-6E,8Z-octadecadienoic acid and 5(S)-oxo-6E,8Z-octadecadienoic acid (5-LO metabolites of sebaleic acid, i.e. 5Z,8Z-octadecadienoic acid); and 5(S)-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic and 5-oxo-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acids (5-LO metabolites of the n-3 polyunsaturated fatty acid, eicosapentaenoic acid). [10]

Antagonists

5-Oxo-12(S)-hydroxy-HETE and its 8-trans isomer, 5-oxo-12(S)-hydroxy-6E,8E,11Z,14Z-eicosatetraenoic acid, and a series of synthetic mimetics of 5-oxo-ETE structure (compounds 346, S-264, S-230, Gue154, and still to be named but considerably more potent drugs than these) block the activity of 5-oxo-ETE but not other stimuli in leukocytes and are presumed to be OXER1 antagonists. [15] [39]

Mechanisms of activating cells

OXE-R couples to the G protein complex Gαi-Gβγ; when bound to a 5-oxo-ETE family member, OXE-R triggers this G protein complex to dissociate into its Gαi and Gβγ components. [7] [8] [35] [40] Gβγ appears to be the component most responsible for activating many of the signal pathways that lead to cellular functional responses. [41] Intracellular cell-activation pathways stimulated by OXER1 include those involving rises in cytosolic calcium ion levels, [34] [42] [43] and along with others that lead to the activation of MAPK/ERK, p38 mitogen-activated protein kinases, cytosolic Phospholipase A2, PI3K/Akt, and protein kinase C beta (i.e. PRKCB1, delta (i.e. PRKCD), epsilon (i.e. PRKCE), and zeta (i.e. PRKCZ). [9] [18] [27] [44] [45] [46] [47]

Function

OXER1 is activated by 5-oxo-ETE, 5-HETE, and other members of the 5-Hydroxyicosatetraenoic acid family of arachidonic acid metabolites and thereby mediates this family's stimulatory effects on cell types that are involved in mediating immunity-based inflammatory reactions such as neutrophils, monocytes, and macrophages) as well as allergic reactions such as eosinophils and basophils. It also mediates the in vitro proliferation and other pro-malignant responses of cultured prostate, breast, ovary, and kidney cancer cells to the 5-HETE family of agonists. These studies suggest that OXER1 may be involved in orchestrating inflammatory and allergic responses in humans and contribute to the growth and spread of human prostate, breast, ovary, and kidney cancers. OXER1 is responsible for steroid production response to 5-oxo-ETE by human steroidogenic cells in vitro and therefore could be involved in steroid production in humans.

To date, however, all studies have been pre-clinical; they use model systems that can suggest but not prove the contribution of OXER1 to human physiology and diseases. The most well-studied and promising area for OXER1 function is in allergic reactions. The recent development of OXER1 antagonists will help address this issue.

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000162881 – Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, Ohnuki T (2002). "Identification of a novel human eicosanoid receptor coupled to G(i/o)". J. Biol. Chem. 277 (35): 31459–65. doi: 10.1074/jbc.M203194200 . PMID   12065583.
  4. 1 2 Brink C, Dahlén SE, Drazen J, Evans JF, Hay DW, Rovati GE, Serhan CN, Shimizu T, Yokomizo T (2004). "International Union of Pharmacology XLIV. Nomenclature for the oxoeicosanoid receptor". Pharmacol. Rev. 56 (1): 149–57. doi:10.1124/pr.56.1.4. PMID   15001665. S2CID   7229884.
  5. ↑ "Entrez Gene: OXER1 oxoeicosanoid (OXE) receptor 1".
  6. ↑ O'Flaherty JT, Taylor JS, Thomas MJ (1998). "Receptors for the 5-oxo class of eicosanoids in neutrophils". J. Biol. Chem. 273 (49): 32535–41. doi: 10.1074/jbc.273.49.32535 . PMID   9829988.
  7. 1 2 Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, Ohnuki T (2002). "Identification of a novel human eicosanoid receptor coupled to G(i/o)". J. Biol. Chem. 277 (35): 31459–31465. doi: 10.1074/jbc.M203194200 . PMID   12065583.
  8. 1 2 Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P (2003). "Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils". Mol. Pharmacol. 63 (3): 471–477. doi:10.1124/mol.63.3.471. PMID   12606753.
  9. 1 2 Hosoi T, Sugikawa E, Chikada A, Koguchi Y, Ohnuki T (2005). "TG1019/OXE, a Galpha(i/o)-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis". Biochem. Biophys. Res. Commun. 334 (4): 987–995. doi:10.1016/j.bbrc.2005.06.191. PMID   16039985.
  10. 1 2 Powell WS, Rokach J (2013). "The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor". Prog. Lipid Res. 52 (4): 651–665. doi:10.1016/j.plipres.2013.09.001. PMC   5710732 . PMID   24056189.
  11. ↑ Koike D, Obinata H, Yamamoto A, Takeda S, Komori H, Nara F, Izumi T, Haga T (2006). "5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G(12/13)". J. Biochem. 139 (3): 543–549. doi: 10.1093/jb/mvj060 . PMID   16567419.
  12. 1 2 Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP (Jun 2011). "International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)". Pharmacological Reviews. 63 (2): 269–90. doi: 10.1124/pr.110.003301 . PMID   21454438.
  13. ↑ Guo Y, Zhang W, Giroux C, Cai Y, Ekambaram P, Dilly AK, Hsu A, Zhou S, Maddipati KR, Liu J, Joshi S, Tucker SC, Lee MJ, Honn KV (Sep 2011). "Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid". The Journal of Biological Chemistry. 286 (39): 33832–40. doi: 10.1074/jbc.M110.216564 . PMC   3190773 . PMID   21712392.
  14. ↑ Powell WS, Rokach J (2013). "The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor". Prog. Lipid Res. 52 (4): 651–65. doi:10.1016/j.plipres.2013.09.001. PMC   5710732 . PMID   24056189.
  15. 1 2 3 Powell WS, Rokach J (2014). "Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid". Biochim. Biophys. Acta. 1851 (4): 340–355. doi:10.1016/j.bbalip.2014.10.008. PMC   5710736 . PMID   25449650.
  16. ↑ Hevko JM, Bowers RC, Murphy RC (2001). "Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid and identification of novel omega-oxidized metabolites in the mouse macrophage". J. Pharmacol. Exp. Ther. 296 (2): 293–305. PMID   11160610.
  17. 1 2 Cooke M, Di Cónsoli H, Maloberti P, Cornejo Maciel F (2013). "Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells". Mol. Cell. Endocrinol. 371 (1–2): 71–8. doi:10.1016/j.mce.2012.11.003. hdl: 11336/8381 . PMID   23159987. S2CID   8520991.
  18. 1 2 O'Flaherty JT, Rogers LC, Chadwell BA, Owen JS, Rao A, Cramer SD, Daniel LW (2002). "5(S)-Hydroxy-6,8,11,14-E,Z,Z,Z-eicosatetraenoate stimulates PC3 cell signaling and growth by a receptor-dependent mechanism". Cancer Res. 62 (23): 6817–9. PMID   12460891.
  19. ↑ Ghosh J, Myers CE (1998). "Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 95 (22): 13182–13187. Bibcode:1998PNAS...9513182G. doi: 10.1073/pnas.95.22.13182 . PMC   23752 . PMID   9789062.
  20. ↑ Rodríguez-Blanco G, Burgers PC, Dekker LJ, Ijzermans JJ, Wildhagen MF, Schenk-Braat EA, Bangma CH, Jenster G, Luider TM (2014). "Serum levels of arachidonic acid metabolites change during prostate cancer progression". Prostate. 74 (6): 618–627. doi:10.1002/pros.22779. PMID   24435810. S2CID   2089553.
  21. 1 2 O'Flaherty JT, Rogers LC, Paumi CM, Hantgan RR, Thomas LR, Clay CE, High K, Chen YQ, Willingham MC, Smitherman PK, Kute TE, Rao A, Cramer SD, Morrow CS (2005). "5-Oxo-ETE analogs and the proliferation of cancer cells". Biochim. Biophys. Acta. 1736 (3): 228–236. doi:10.1016/j.bbalip.2005.08.009. PMID   16154383.
  22. ↑ Grant GE, Rubino S, Gravel S, Wang X, Patel P, Rokach J, Powell WS (2011). "Enhanced formation of 5-oxo-6,8,11,14-eicosatetraenoic acid by cancer cells in response to oxidative stress, docosahexaenoic acid and neutrophil-derived 5-hydroxy-6,8,11,14-eicosatetraenoic acid". Carcinogenesis. 32 (6): 822–828. doi:10.1093/carcin/bgr044. PMC   3146358 . PMID   21393477.
  23. ↑ Avis IM, Jett M, Boyle T, Vos MD, Moody T, Treston AM, Martínez A, Mulshine JL (1996). "Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling". J. Clin. Invest. 97 (3): 806–813. doi:10.1172/JCI118480. PMC   507119 . PMID   8609238.
  24. ↑ Paige M, Saprito MS, Bunyan DA, Shim YM (2009). "HPLC quantification of 5-hydroxyeicosatetraenoic acid in human lung cancer tissues". Biomed. Chromatogr. 23 (8): 817–21. doi:10.1002/bmc.1191. PMID   19353686.
  25. ↑ Freedman RS, Wang E, Voiculescu S, Patenia R, Bassett RL, Deavers M, Marincola FM, Yang P, Newman RA (2007). "Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer". Clin. Cancer Res. 13 (19): 5736–44. doi:10.1158/1078-0432.CCR-07-0583. PMID   17908963. S2CID   6450879.
  26. ↑ Hussey HJ, Tisdale MJ (1996). "Inhibition of tumour growth by lipoxygenase inhibitors". Br. J. Cancer. 74 (5): 683–687. doi:10.1038/bjc.1996.422. PMC   2074717 . PMID   8795568.
  27. 1 2 Ding XZ, Tong WG, Adrian TE (2003). "Multiple signal pathways are involved in the mitogenic effect of 5(S)-HETE in human pancreatic cancer". Oncology. 65 (4): 285–294. doi:10.1159/000074640. PMID   14707447. S2CID   22159108.
  28. ↑ Ding XZ, Iversen P, Cluck MW, Knezetic JA, Adrian TE (1999). "Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells". Biochem. Biophys. Res. Commun. 261 (1): 218–23. doi:10.1006/bbrc.1999.1012. PMID   10405349.
  29. ↑ Powell WS, Rokach J (Apr 2015). "Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (4): 340–355. doi:10.1016/j.bbalip.2014.10.008. PMC   5710736 . PMID   25449650.
  30. ↑ Cossette C, Gravel S, Reddy CN, Gore V, Chourey S, Ye Q, Snyder NW, Mesaros CA, Blair IA, Lavoie JP, Reinero CR, Rokach J, Powell WS (Aug 2015). "Biosynthesis and actions of 5-oxoeicosatetraenoic acid (5-oxo-ETE) on feline granulocytes". Biochem Pharmacol. 96 (3): 247–55. doi:10.1016/j.bcp.2015.05.009. PMC   4830392 . PMID   26032638.
  31. ↑ Ahmed K, Tunaru S, Offermanns S (2009). "GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors". Trends Pharmacol. Sci. 30 (11): 557–62. doi:10.1016/j.tips.2009.09.001. PMID   19837462.
  32. ↑ Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP (2011). "International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)". Pharmacol. Rev. 63 (2): 269–90. doi: 10.1124/pr.110.003301 . PMID   21454438.
  33. 1 2 O'Flaherty JT, Taylor JS, Thomas MJ (1998). "Receptors for the 5-oxo class of eicosanoids in neutrophils". J. Biol. Chem. 273 (49): 32535–41. doi: 10.1074/jbc.273.49.32535 . PMID   9829988.
  34. 1 2 O'Flaherty JT, Nishihira J (1987). "5-Hydroxyeicosatetraenoate promotes Ca2+ and protein kinase C mobilization in neutrophils". Biochem. Biophys. Res. Commun. 148 (2): 575–81. doi:10.1016/0006-291X(87)90915-6. PMID   3689361.
  35. 1 2 O'Flaherty JT, Rossi AG (1993). "5-hydroxyicosatetraenoate stimulates neutrophils by a stereospecific, G protein-linked mechanism". J. Biol. Chem. 268 (20): 14708–14. doi: 10.1016/S0021-9258(18)82391-2 . PMID   8392058.
  36. ↑ Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P (2003). "Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils". Mol. Pharmacol. 63 (3): 471–7. doi:10.1124/mol.63.3.471. PMID   12606753.
  37. ↑ Hosoi T, Sugikawa E, Chikada A, Koguchi Y, Ohnuki T (2005). "TG1019/OXE, a Galpha(i/o)-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis". Biochem. Biophys. Res. Commun. 334 (4): 987–95. doi:10.1016/j.bbrc.2005.06.191. PMID   16039985.
  38. ↑ Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE (2014). "Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7". Br. J. Pharmacol. 171 (15): 3551–74. doi:10.1111/bph.12665. PMC   4128057 . PMID   24588652.
  39. ↑ Konya V, Blättermann S, Jandl K, Platzer W, Ottersbach PA, Marsche G, Gütschow M, Kostenis E, Heinemann A (2014). "A biased non-Gαi OXE-R antagonist demonstrates that Gαi protein subunit is not directly involved in neutrophil, eosinophil, and monocyte activation by 5-oxo-ETE". J. Immunol. 192 (10): 4774–82. doi: 10.4049/jimmunol.1302013 . PMID   24733850.
  40. ↑ O'Flaherty JT, Taylor JS, Thomas MJ (1998). "Receptors for the 5-oxo class of eicosanoids in neutrophils". J. Biol. Chem. 273 (49): 32535–32541. doi: 10.1074/jbc.273.49.32535 . PMID   9829988.
  41. ↑ Ramos TN, Bullard DC, Barnum SR (2014). "ICAM-1: isoforms and phenotypes". J. Immunol. 192 (10): 4469–74. doi:10.4049/jimmunol.1400135. PMC   4015451 . PMID   24795464.
  42. ↑ Rossi AG, Thomas MJ, O'Flaherty JT (1988). "Stereospecific bioactions of 5-hydroxyeicosatetraenoate". FEBS Lett. 240 (1–2): 163–6. doi: 10.1016/0014-5793(88)80360-0 . PMID   3191990. S2CID   43027447.
  43. ↑ O'Flaherty JT, Cordes J, Redman J, Thomas MJ (1993). "5-Oxo-eicosatetraenoate, a potent human neutrophil stimulus". Biochem. Biophys. Res. Commun. 192 (1): 129–34. doi:10.1006/bbrc.1993.1391. PMID   8386504.
  44. ↑ Wijkander J, O'Flaherty JT, Nixon AB, Wykle RL (1995). "5-Lipoxygenase products modulate the activity of the 85-kDa phospholipase A2 in human neutrophils". J. Biol. Chem. 270 (44): 26543–26549. doi: 10.1074/jbc.270.44.26543 . PMID   7592874.
  45. ↑ Sarveswaran S, Thamilselvan V, Brodie C, Ghosh J (2011). "Inhibition of 5-lipoxygenase triggers apoptosis in prostate cancer cells via down-regulation of protein kinase C-epsilon". Biochim. Biophys. Acta. 1813 (12): 2108–17. doi:10.1016/j.bbamcr.2011.07.015. PMC   3541030 . PMID   21824498.
  46. ↑ Sarveswaran S, Ghosh J (2013). "OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells". Cancer Lett. 336 (1): 185–95. doi:10.1016/j.canlet.2013.04.027. PMC   3892773 . PMID   23643940.
  47. ↑ Langlois A, Chouinard F, Flamand N, Ferland C, Rola-Pleszczynski M, Laviolette M (2009). "Crucial implication of protein kinase C (PKC)-delta, PKC-zeta, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils". J. Leukoc. Biol. 85 (4): 656–63. doi: 10.1189/jlb.0808492 . PMID   19164129. S2CID   28897173.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.