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Cancer and Metastasis Reviews

, Volume 13, Issue 3–4, pp 241–256 | Cite as

Regulation of prostaglandin synthase-1 and prostaglandin synthase-2

  • Harvey R. Herschman
  • Warren Hall
Article

Abstract

It has been assumed that the rate-limiting step in the ligand-induced synthesis of prostaglandins is the release of arachidonic acid from membrane phospholipid stores as a result of the activation of phospholipase. The assumption has been that the arachidonic acid is converted to PGH2 by the constitutive prostaglandin synthase/cyclooxygenase EC1.14.99.1 (PGS-1) enzyme present in cells. In this model, PGS-1 is proposed to be present in excess, and the production of arachidonic acid is thought to be rate limiting. However, a second prostaglandin synthase gene, PGS-2 has recently been described. The PGS-2 gene is induced by a variety of ligands, in cells as diverse as fibroblasts, monocytes, macrophages, smooth muscle cells, ovarian granulosa cells, epithelial cells, endothelial cells, and neurons. Moreover, PGS-2 induction is inhibited in nearly all contexts by glucocorticoids. It seems likely, therefore, that the regulation of PGS-2 expression plays a critical role in the production of prostanoids, both in normal physiological processes and in pathophysiological processes involving these paracrine mediators. In this review, we consider the regulation of the two genes, PGS-1 and PGS-2, that encode the isoforms of prostaglandin synthase.

Key words

prostaglandin prostaglandin synthase cyclooxygenase eicosanoids TIS10 

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References

  1. 1.
    Thun MJ, Namboodiri MM, Heath CW Jr: Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325: 1593–1596, 1991Google Scholar
  2. 2.
    Kune GA, Kune S, Watson LF: Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48: 4399–4404, 1988Google Scholar
  3. 3.
    Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD, Shapiro S: A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of the large-bowel cancer. J Natl Cancer Inst 83: 355–358, 1991Google Scholar
  4. 4.
    Smith WL, Marnett LJ: Prostaglandin endoperoxide synthase: structure and catalysis. Biochim Biophys Acta 1083: 1–17, 1991Google Scholar
  5. 5.
    Hemler M, Lands WEM, Smith WL: Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J Biol Chem 251: 5575–5579, 1976Google Scholar
  6. 6.
    Miyamoto T, Ogino N, Yamamoto S, Hayaishi O: Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem 251: 2629–2636, 1976Google Scholar
  7. 7.
    VanDerOuderaa FJ, Buytenhek M, Nugteren DH, Van-Dorp DA: Purification and characterization of prostaglandin synthetase from sheep vesicular glands. Biochim Biophys Acta 487: 315–331, 1977Google Scholar
  8. 8.
    DeWitt DL, Smith WL: Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. Proc Natl Acad Sci 85: 1412–1416, 1988Google Scholar
  9. 9.
    Merlie JP, Fagan D, Mudd J, Needleman P: Isolation and characterization of the complementary DNA for sheep seminal vesicle prostaglandin endoperoxide synthase (cyclooxygenase). J Biol Chem 263: 3550–3553, 1988Google Scholar
  10. 10.
    Yokayama C, Takai T, Tanabe T: Primary structure of sheep prostaglandin endoperoxide synthase deduced from cDNA sequence. FEBS Lett 231: 347–351, 1988Google Scholar
  11. 11.
    DeWitt DL, El-Harith EA, Kraemer SA, Andrews MJ, Yao EF, Armstrong RL, Smith WL: The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. J Biol Chem 265: 5192–5198, 1990Google Scholar
  12. 12.
    Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA: Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J 5: 2304–2312, 1991Google Scholar
  13. 13.
    DeWitt DL: Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta 1083: 121–134, 1991Google Scholar
  14. 14.
    Raz A, Wyche A, Siegel N, Needleman P: Regulation of fibroblast cyclooxygenase synthesis by interleukin-1. J Biol Chem 263: 3022–3025, 1988Google Scholar
  15. 15.
    Raz A, Wyche A, Needleman P: Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases. Proc Natl Acad Sci 86: 1657–1661, 1989Google Scholar
  16. 16.
    Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P: The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem 265: 16737–16740, 1990Google Scholar
  17. 17.
    Masferrer JL, Zweifel BS, Seibert K, Needleman P: Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 86: 1375–1379, 1990Google Scholar
  18. 18.
    Rosen GD, Birkenmeier TM, Raz A, Holtzman MJ: Identification of cyclooxygenase-related gene and its potential role in prostaglandin formation. Biochem Biophys Res Commun 164: 1358–1365, 1989Google Scholar
  19. 19.
    Wong WYL, DeWitt DL, Smith WL, Richards JS: Rapid induction of prostaglandin endoperoxide synthase in rat preovulatory follicles by luteinizing hormone and cAMP is blocked by inhibitors of transcription and translation. Molecular Endocrinology 3: 1714–1723, 1989Google Scholar
  20. 20.
    Sirois J, Richards JS: Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles. J Biol Chem 267: 6383–6388, 1992Google Scholar
  21. 21.
    Barker K, Aderem A, Hanafusa H: Modulation of arachidonic acid metabolism by Rous sarcoma virus. J Virol 63: 2929–2935, 1989Google Scholar
  22. 22.
    Han JW, Sadowski H, Young DA, Macara IG: Persistent induction of cyclooxygenase in p60v-src-transformed 3T3 fibroblasts. Proc Natl Acad Sci 87: 3373–3377, 1990Google Scholar
  23. 23.
    Xie W, Chipman JG, Robertson DL, Erikson RL, Simmons DL: Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci 88: 2692–2696, 1991Google Scholar
  24. 24.
    Lim RW, Varnum BC, Herschman HR: Cloning of tetradecanoyl phorbol ester induced ‘primary response’ sequences and their expression in density-arrested Swiss 3T3 cells and a TPA nonproliferative variant. Oncogene 1: 263–270, 1987Google Scholar
  25. 25.
    Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR: TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266: 12866–12872, 1991Google Scholar
  26. 26.
    Fletcher BS, Kujubu DA, Perrin DM, Herschman HR: Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase. J Biol Chem 267: 4338–4344, 1992Google Scholar
  27. 27.
    O'Banion MK, Winn VD, Young DA: cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci 89: 4888–4892, 1992Google Scholar
  28. 28.
    Meade EA, Smith WL, DeWitt DL: Expression of the murine prostaglandin (PGH) synthase-2 isozymes in cos-1 cells. J Lipid Mediators 6: 119–129, 1993Google Scholar
  29. 29.
    Ping XW, Warden C, Fletcher BS, Kujubu DA, Herschman HR, Lusis AL: Chromosomal organization of the inducible and constitutive prostaglandin synthase/cyclooxygenase genes in mouse. Genomics 15: 458–460, 1993Google Scholar
  30. 30.
    Qureshi SA, Joseph CK, Rim M, Maroney A, Foster DA: v-Src activates both protein kinase C-dependent and independent signaling pathways in murine fibroblasts. Oncogene 6: 995–999, 1991Google Scholar
  31. 31.
    Kujubu DA, Reddy ST, Fletcher BS, Herschman HR: Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells. J Biol Chem 268: 5425–5430, 1993Google Scholar
  32. 32.
    O'Banion MK, Sadowski HB, Winn V, Young DA: A serumand glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 266: 23261–23267, 1991Google Scholar
  33. 32a.
    Ryseck RP, Raynoscheck C, Macdonald-Bravo H, Dorfman K, Mattei M, Bravo R: Identification of an immediate early gene, phs-B, whose protein prodet has prostaglandin synthase/cyclooxygenase activity. Cell Growth Differ 3: 443–450, 1992Google Scholar
  34. 33.
    Sirois J, Levy LO, Simmons DL, Richards JS: Characterization and hormonal regulation of the promoter of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. J Biol Chem 268: 12199–12206, 1993Google Scholar
  35. 34.
    Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci 89: 7384–7385, 1992Google Scholar
  36. 35.
    Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM: Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem 268: 9049–9054, 1993Google Scholar
  37. 36.
    Kraemer SA, Meade EA, DeWitt DL: Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5′-flanking regulatory sequences. Arch Biochem Biophys 293: 391–400, 1992Google Scholar
  38. 37.
    Yokoyama C, Tanabe T: Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme. Biochem Biophys Res Commun 165: 888–894, 1989Google Scholar
  39. 38.
    Xie W, Merrill JR, Bradshaw WS, Simmons DL: Structural determination and promoter analysis of the chicken mitogen-inducible prostaglandin G/H synthase gene and genetic mapping of the murine homolog. Arch Biochem Biophys 300: 247–252, 1993Google Scholar
  40. 39.
    Herschman HR: Primary response genes induced by growth factors and tumor promoters. In: Richardson CC, Abelson JN, Meister A, Walsh CT (eds) Annual Review of Biochem, vol. 60. Annual Reviews, Inc., Palo Alto, California, 1991, pp 281–319Google Scholar
  41. 40.
    Kujubu DA, Herschman HR: Dexamathasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene. J Biol Chem 267: 7991–7994, 1992Google Scholar
  42. 41.
    Herschman HR, Kujubu DA, Fletcher GS, Ma Q-F, Varnum BC, Gilbert RS, Reddy ST: The TIS genes primary response genes induced by growth factors and tumor promoters. In: Cohen W, Moldave K (eds) Progress in Nucleic Acids Research and Molecular Biology. Academic Press, Orlando, Florida, p 115–148 (1994)Google Scholar
  43. 42.
    O'Neill GP, Ford-Hutchinson AW: Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. Fed, European Biochem Soc 330: 156–160, 1993Google Scholar
  44. 43.
    Sirois J, Simmons DL, Richards JS: Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. J Biol Chem 267: 11586–11592, 1992Google Scholar
  45. 44.
    Varnum BC, Lim RW, Kujubu DA, Luner S, Kaufman SE, Greenberger JS, Gasson JC, Herschman HR: Granulocyte-macrophage colony-stimulating factor and tetradecanoyl phorbol acetate induce a distinct, restricted subset of primary-response TIS genes in both proliferating and terminally differentiated myeloid cells. Mol Cell Biol 9: 3580–3583, 1989Google Scholar
  46. 45.
    Phillips TA, Kujubu DA, Mackay RJ, Herschman HR, Russell SW, Pace JL: The mouse macrophage activation-associated marker protein p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase). J Leukocyte Biol 53: 411–419, 1993Google Scholar
  47. 46.
    O'Sullivan MG, Huggins Jr EM, McCall CE: Lipopolysac-charide-induced expression of prostaglandin H synthase-2 in alveolar macrophages is inhibited by dexamethasone but not by aspirin. Biochem Biophys Res Commun 191: 1294–1300, 1993Google Scholar
  48. 47.
    Hoff T, DeWitt D, Kaever V, Resch K, Coppelt-Struebe M: Differentiation-associated expression of prostaglandin G/H synthase in monocytic cells. Fed European Biochem-Soc 320: 38–42, 1993Google Scholar
  49. 48.
    Hamasaki Y, Kitzler J, Hardman R, Nettesheim P, Eling TE: Phorbol ester and epidermal growth factor enhance the expression of two inducible prostaglandin H synthase genes in rat tracheal epithelial cells. Arch Biochem Biophys 304: 226–234, 1993Google Scholar
  50. 49.
    Sano H, Hla T, Maier JAM, Crofford LJ, Case JP, Maciag T, Weiler RL:In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest, Inc. 89: 97–108, 1992Google Scholar
  51. 50.
    Lyons-Giordano B, Pratta MA, Galbraith W, Davis GL, Arner EC: Interleukin-1 differentially modulates chondrocyte expression of cyclooxygenase-2 and phospholipase A2. Experimental Cell Res 206: 58–62, 1993Google Scholar
  52. 51.
    Habib A, Creminon C, Frobert Y, Grassi J, Pradelles P, Maclouf J: Demonstration of an inducible cyclooxygenase in human endothelial cells using antibodies raised against the carboxyl-terminal region of the cyclooxygenase-2. J Biol Chem 268: 23448–23454, 1993Google Scholar
  53. 52.
    Yamamoto K, Alberts B: Steroid receptors: elements for modulation of eukaryotic transcription. Ann Rev Biochem 45: 721–746, 1976Google Scholar
  54. 53.
    Arenander AT, Herschman HR: Primary response gene expression in the nervous system. In: Fallon JH, Loughlin SE (eds) Neurotrophic Factors. Academic Press, New York, 1992, pp 89–123Google Scholar
  55. 54.
    Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF: Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 11: 371–386, 1993Google Scholar
  56. 55.
    Yokota K, Kusaka M, Ohshima T, Yamamoto S, Kurihara N, Yoshino T, Kumegawa M: Stimulation of prostaglandin E2 synthesis in cloned osteoblastic cells of mouse (MC3T3-E1) by epidermal growth factor. J Biol Chem 261: 15410–15415, 1986Google Scholar
  57. 56.
    Kusaka M, Oshima T, Yokota K, Yamamoto S, Kumegawa M: Possible induction of fatty acid cyclooxygenase in mouse osteoblastic cells (MC3T3-E1) by cAMP. Biochim Biophys Acta 972: 339–346, 1988Google Scholar
  58. 57.
    Oshima T, Yoshimoto T, Yamamoto S, Kumegawa M, Yokoyama C, Tanabe T: cAMP-dependent induction of fatty acid cyclooxygenase mRNA in mouse osteoblastic cells (MC3T3-E1). J Biol Chem 266: 13621–13626, 1991Google Scholar
  59. 58.
    Phlbeam CC, Kawaguchi H, Hakeda Y, Voznesensky O, Alander CB, Raisz LG: Differential regulation of inducible and constitutive prostaglandin endoperoxide synthase in osteoblastic MC3T3-E1 cells. J Biol Chem 268: 25643–25649, 1993Google Scholar
  60. 59.
    Lin AH, Bienkowski MJ, Gorman RR: Regulation of prostaglandin H synthase mRNA levels and prostaglandin biosynthesis by platelet-derived growth factor. J Biol Chem 264: 17379–17383, 1989Google Scholar
  61. 60.
    Maier JAM, Hla T, Maciag T: Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells. J Biol Chem 265: 10805–10808, 1990Google Scholar
  62. 61.
    Koehler L, Hass R, DeWitt DL, Resch K, Coppelt-Struebe M: Glucocorticoid-induced reduction of prostanoid synthesis in TPA-differentiated U937 cells is mainly due to a reduced cyclooxygenase activity. Biochem Pharmacology 40: 1307–1316, 1990Google Scholar
  63. 62.
    Smith CJ, Morrow JD, Roberts II LJ, Marnett LJ: Differentiation of monocytoid THP-1 cells with phorbol ester induces expression of prostaglandin endoperoxide synthase (COX-1). Biochem Biophys Res Commun 192: 787–793, 1993Google Scholar
  64. 63.
    Diaz A, eginato AM, Jimenez SA: Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor β1, interleukin 1β, and tumor necrosis factor α. J Biol Chem 267: 10816–10821, 1992Google Scholar
  65. 64.
    Masferrer JL, Seibert K, Zweifel B, Needleman P: Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci 89: 3917–3921, 1992Google Scholar
  66. 65.
    Masferrer JL, Reddy ST, Zweifel B, Seibert K, Needleman P, Gilbert RS, Herschman HR:In vivo regulation of cyclooxygenase-2 by glucocorticoids in peritoneal macrophages. J Pharm Expt Ther, in pressGoogle Scholar
  67. 66.
    Regier MK, DeWitt DL, Schindler MS, Smith WL: Subcellular localization of prostaglandin endoperoxide synthase-2 in murine 3T3 cells. Arch Biochem Biophys 301: 439–444, 1993Google Scholar
  68. 67.
    Meade EA, Smith WL, DeWitt DL: Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem 268: 6610–6614, 1993Google Scholar
  69. 68.
    Reddy ST, Herschman HR: Ligand-induced prostaglandin synthesis requires expression of the TIS10/PGS-2 prostaglandin synthase gene in murine fibroblasts and macrophages. J Biol Chem 269: 15473–15480, 1994Google Scholar
  70. 69.
    Miller DK, Gillard JW, Vickers PJ, Sadowski S, Leveille C, Mancini JA, Charleston P, Dixon RAF, Ford-Hutchinson AW, Fortin R, Gauthier J, Rodkey J, Rosen R, Rouzer C, Segal IS, Strander C, Evans JF: Identification and isolation of a membrane protein necessary for leukotriene production. Nature 343: 278–281, 1990Google Scholar
  71. 70.
    Dixon RAF, Diehl RE, Opas E, Rands E, Vickers PJ, Evans JF, Gillard JW, Miller DK: Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature 343: 282–284, 1990Google Scholar
  72. 71.
    Reid GK, Kargman S, Vickers PJ, Mancini JA, Leveille C, Ethier D, Miller DK, Gillard JW, Dixon AF, Evans JF: Correlation between expression of 5-lipoxygenase-activating protein, 5-lipoxygenase, and cellular leukotriene synthesis. J Biol Chem 265: 19818–19823, 1990Google Scholar
  73. 72.
    Wang LH, Hajibeigi A, Xu XM, Loose-Mitchell D, Wu KK: Characterization of the promoter of human prostaglandin H synthase-1 gene. Biochem Biophys Res Commun 190: 406–411, 1993Google Scholar
  74. 73.
    Sirois J, Richards AS: Transcriptional regulation of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. J Biol Chem 268: 21931–21938, 1993Google Scholar
  75. 73a.
    Xie W, Fletcher BS, Andersen RD, Herschman HR:v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE treanscription response element. Mol Cell Biol (in press)Google Scholar
  76. 74.
    Reddy ST, Gilbert RS, Xie W, Luner S, Herschman HR: TGF-Beta1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages. J Leukocyte Biol 55: 192–200, 1994Google Scholar
  77. 75.
    Gilbert RS, Reddy ST, Kujubu DA, Xie W, Luner S, Herschman HR: TGF-Beta1 augments mitogen-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene both in Swiss 3T3 cells and in murine embryo fibroblasts. J Cell Physiol 159: 67–75, 1994Google Scholar
  78. 76.
    Gilbert RS, Herschman HR: Macrophage nitric oxide synthase is a glucocorticoid-inhibitable primary response gene in 3T3 cells. J Cell Physiol 157: 128–134, 1993Google Scholar
  79. 77.
    Gilbert RS, Herschman HR: Transforming growth factor beta differentially modulates the inducible nitric oxide synthase gene in distinct cell types. Biochem Biophys Res Commun 195: 380–384, 1993Google Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Harvey R. Herschman
    • 1
  • Warren Hall
    • 2
  1. 1.Department of Biological Chemistry and Laboratory of Structural Biology and Molecular MedicineCenter for the Health Sciences, University of CaliforniaLos AngelesUSA
  2. 2.UCLALos AngelesUSA

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