Induction of HSP70 by Prostaglandins

  • M. Gabriella Santoro
  • Enrico Garaci
  • Carla Amici


Prostaglandins (PGs) are a class of naturally occurring cyclic 20-carbon fatty acids, synthesized by most types of eukaryotic cells from polyunsaturated fatty acid precursors. Arachidonic acid (eicosatetraenoic acid) is the major source of PGs in mammalian tissue, together with eicosatrienoic and eicosapentaenoic acids from the phospholipid pool of the cell membrane, from which they are released in response to external stimuli through the action of phospholipase A and a phosphatidylinositol-specific phospholipase C (reviewed by Samuelsson 1982). PGs are designated by groups, depending on the structure of the cyclopentane ring, and are characterized as mono-, bi- and tri-unsaturated compounds, depending on the number of C-C double bonds in the aliphatic side chains.


Heat Shock Protein K562 Cell Newcastle Disease Virus Sendai Virus African Green Monkey Kidney 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amici C, Benedetto A, Garaci E, Santoro MG (1988) Prostaglandins of the A and J series inhibit herpes simplex virus II replication in vitro. In: 6th Mediterr Congr Chemotherapy, 22–27 May 1988, Taormina, Italy, (Abstr) p 215Google Scholar
  2. Ankel H, Mittnacht S, Jacobsen H (1985) Antiviral activity of Prostaglandin A on encephalomyo-carditis virus-infected cells: a unique effect unrelated to interferon. J Gen Virol 66:2355–2364PubMedCrossRefGoogle Scholar
  3. Benavente J, Esteban M, Jaffe BM, Santoro MG (1984) Selective inhibition of viral gene expression as the mechanism of the antiviral action of PGA1 in vaccinia virus-infected cells. J Gen Virol 65:599–608PubMedCrossRefGoogle Scholar
  4. Bhuyan BK, Adams EG, Badiner GJ, Li LH, Barden K (1986) Cell cycle effects of prostaglandins A1, A2 and D2 in human and murine melanoma cells in culture. Cancer Res 46:1688–1693PubMedGoogle Scholar
  5. Bond U, Schlesinger MJ (1987) Heat-shock proteins and development. Adv Genet 24:1–29PubMedCrossRefGoogle Scholar
  6. Bregman MD, Funk C, Fukushima M (1986) Inhibition of human melanoma growth by prostaglandin A, D and J analogues. Cancer Res 46:2740–2744PubMedGoogle Scholar
  7. Breitman TR (1987) The role of prostaglandins and other arachidonic acid metabolites in the differentiation of HL-60. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in Cancer Research. Springer, Berlin Heidelberg New York Tokyo, pp 161–171Google Scholar
  8. Burdon RH (1982) The human heat-shock proteins: their induction and possible intracellular functions. In: Schlesinger MJ, Ashburner M, Tissieres A (eds) Heat shock from bacteria to man. Cold Spring Harbor Lab, New York, pp 283–288Google Scholar
  9. Carper SW, Duffy JJ, Geraer EW (1987) Heat shock proteins in thermotolerance and other cellular processes. Cancer Res 47:5249–5255PubMedGoogle Scholar
  10. Chen BD, Sapareto SA, Chou T (1987) Induction of prostaglandins production by hyperthermia in murine peritoneal exudate macrophages. Cancer Res 47:11–15PubMedGoogle Scholar
  11. Choppin PW, Scheid A (1980) The role of viral glycoproteins in adsorption, penetration and pathogenicity of viruses. Rev Infect Dis 2:40–61PubMedCrossRefGoogle Scholar
  12. Coceani F, Bishai L, Lees J, Sirko S (1989) Prostaglandin E2 in the pathogenesis of pyrogen fever: validation of an intermediary role. In: Samuelsson B, Wong PYK, Sun FF (eds) Advances in prostaglandins, thromboxane and leukotriene research, Vol 19. Raven Press, New York, pp 394–397Google Scholar
  13. Collins PL, Hightower L (1982) Newcastle Disease Virus stimulates the cellular accumulation of stress (heat shock) proteins. J Virol 44:703–707PubMedGoogle Scholar
  14. Craig EA, Jacobsen K (1985) Mutations in cognate genes of Saccharomyces cerevisiae hsp70 result in reduced growth rates at low temperatures. Mol Cell Biol 5:3517–3524PubMedGoogle Scholar
  15. Dinarello CA, Wolff SM (1982) Molecular basis of fever in humans. Am J Med 72:799–819PubMedCrossRefGoogle Scholar
  16. D’Onofrio C, Bonmassar E, Santoro MG (1989) Inhibition of HTLV-I infection in vitro by antiviral prostaglandins A and J. Pharmacol Res 21:665–666CrossRefGoogle Scholar
  17. D’Onofrio C, Alvino E, Garaci E, Bonmassar E, Santoro MG (1990a) Selection of HTLV-I positive clones is prevented by prostaglandin A in infected cord blood cultures. Br J Cancer 61:207–214PubMedCrossRefGoogle Scholar
  18. D’Onofrio C, Amici C, Bonmassar E, Santoro MG (1990b) The antiproliferative effect of prostaglandins A and J on HTLV-I transformed cells is associated with induction of a heat shock protein. Pharmacol Res (in press)Google Scholar
  19. Ferris DK, Harel-Bellan A, Morimoto R, Welch WJ, Farrar WI (1988) Mitogens and lymphokine stimulation of heat shock proteins in T lymphocytes. Proc Natl Acad Sci USA 85:3850–3854PubMedCrossRefGoogle Scholar
  20. Fukushima M, Kato I, Narumiya S et al. (1989) Prostaglandins A and J: antitumor and antiviral prostaglandins. In: Samuelsson B, Wong PY, Sun FF (eds) Advances in prostaglandins, thromboxane and leukotriene research, Vol 19. Raven Press, New York, pp 415–418Google Scholar
  21. Garaci E, Paoletti R, Santoro MG (1987) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo.Google Scholar
  22. Garry RF, Emin TU, Bose HR (1983) Induction of stress proteins in Sindbis virus- and vesicular stomatitis virus-infected cells. Virology 129:319–332PubMedCrossRefGoogle Scholar
  23. Honma Y, Kasukabe T, Hozumi M, Koshihara Y (1980) Regulation of prostaglandin synthesis during differentiation of cultured mouse myeloid leukemia cells. J Cell Physiol 104:349–357PubMedCrossRefGoogle Scholar
  24. Hughes-Fulford M (1987) The mechanism of prostaglandin inhibition on the cell cycle. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo, pp 115–128Google Scholar
  25. Hughes-Fulford M, Wu J, Kato T, Fukushima M (1985) Inhibition of DNA synthesis and cell cycle by prostaglandins independent of cyclic AMP. In: Hayaishi O, Yamamoto S (eds) Advances in prostaglandins, thromboxane and leukotriene research, Vol 15. Raven Press, New York, pp 401–404Google Scholar
  26. Iida H, Yahara I (1984a) Specific early-G1 blocks accompanied with stringent response in Saccharomyces cerevisiae lead to growth arrest in resting state similar to the Go of higher eukaryotes. J Cell Biol 98:1185–1193PubMedCrossRefGoogle Scholar
  27. Iida H, Yahara I (1984b) Durable synthesis of high molecular weight heat shock proteins in Go cells of the yeast and other eukaryotes. J Cell Biol 99:199–207PubMedCrossRefGoogle Scholar
  28. Johnson GS, Pastan I (1971) Change in growth and morphology of fibroblast by prostaglandins. J Natl Cancer Inst 47:1357–1360PubMedGoogle Scholar
  29. Kaczmarek L, Calabretta B, Kao H, Heintz N, Nevins J, Baserga R (1987) Control of hsp70 RNA levels in human lymphocytes. J Cell Biol 104:183–187PubMedCrossRefGoogle Scholar
  30. Kao H, Nevins JR (1983) Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol 3:2058–2065PubMedGoogle Scholar
  31. Kao H, Capasso O, Heintz N, Nevins JR (1985) Cell cycle control of the human HSP70 gene: implications for the role of a cellular ElA-like function. Mol Cell Biol 5:628–633PubMedGoogle Scholar
  32. Karmali R, Schiller P, Horrobin DF (1976) Prostaglandins can prevent the binding of chloroquine to calf thymus DNA. Prostaglandins 12:463–469PubMedCrossRefGoogle Scholar
  33. Khandjian EW, Turler H (1983) Simian virus 40 and polyoma virus induce the synthesis of heat shock proteins in permissive cells. Mol Cell Biol 3:1–8PubMedGoogle Scholar
  34. Kingston RE, Baldin AS, Sharp PA (1984) Regulation of heat-shock protein 70 gene expression by c-myc. Nature (Lond) 312:280–282CrossRefGoogle Scholar
  35. Lin MC, Segawa K, Ito Y, Beckner SK (1986) The effect of viral transformation on prostaglandin production depends on the cell type. Virology 155:19–26PubMedCrossRefGoogle Scholar
  36. Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45:321–334PubMedGoogle Scholar
  37. Marini S, Palamara AT, Garaci E, Santoro MG (1990) Growth inhibition of Friend erythroleukemia cell tumours in vivo by a synthetic analogue of prostaglandin A: an action independent of natural killer activity. Br J Cancer 61:394–399PubMedCrossRefGoogle Scholar
  38. Milarski KL, Morimoto R (1986) Expression of human HSP70 during the synthetic phase of the cell cycle. Proc Natl Acad Sci USA 83:9517–9521PubMedCrossRefGoogle Scholar
  39. Moore MAS (1982) G-CSF: its relationship to leukemia differentiation-inducing activity and other hemopoietic regulators. J Cell Physiol 1:53–64CrossRefGoogle Scholar
  40. Narumiya S, Fukushima M (1985) Δ12-prostaglandin J2, an ultimate metabolite of prostaglandin D2 exerting cell growth inhibition. Biochem Biophys Res Commun 127:739–745PubMedCrossRefGoogle Scholar
  41. Narumiya S, Fukushima M (1986) Site and mechanism of growth inhibition by prostaglandins. I. Active transport and intracellular accumulation of cyclopentenone prostaglandins, a reaction leading to growth inhibition. J Pharmacol Exp Ther 293:500–505Google Scholar
  42. Narumiya S, Ohno K, Fujiwara M, Fukushima M (1986) Site and mechanism of growth inhibition by prostaglandins. II. Temperature-dependent transfer of cyclopentenone prostaglandin to nuclei. J Pharmacol Exp Ther 293:506–511Google Scholar
  43. Narumiya S, Ohno K, Fukushima M, Fujiwara M (1987) Cellular uptake and nuclear accumulation of prostaglandin A and J, a mechanism of prostaglandin-induced growth inhibition. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo, pp 86–96Google Scholar
  44. Nevins JR (1982) Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell 29:913–919PubMedCrossRefGoogle Scholar
  45. Ninnemann JL (1988) Prostaglandins, leukotrienes and the immune response. Cambridge Univ Press, Cambridge New YorkCrossRefGoogle Scholar
  46. Notarianni EL, Preston CM (1982) Activation of cellular stress protein genes by herpes simplex virus temperature-sensitive mutants which overproduce early polypeptides. Virol 123:113–122CrossRefGoogle Scholar
  47. Ohno K, Fujiwara M, Fukushima M, Narumiya S (1986) Metabolic dehydration of prostaglandin E2 and cellular uptake of the dehydration product: correlation with prostaglandin E2-induced growth inhibition. Biochem Biophys Res Commun 139:808–815PubMedCrossRefGoogle Scholar
  48. Ohno K, Fukushima M, Fujiwara M, Narumiya S (1988) Induction of 68,000 dalton heat shock proteins by cyclopentenone prostaglandins. J Biol Chem 263:19764–19770PubMedGoogle Scholar
  49. Olsson IL, Breitman TR, Gallo RC (1982) Priming of human myeloid leukemia cell line HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3’:5’-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor. Cancer Res 42:3928–3933PubMedGoogle Scholar
  50. Palamara AT, Pica F, Amici C, Figna L, Garaci E, Santoro MG (1989) In vitro and in vivo antiviral activity of delta 12-prostaglandin J2. In: Int Symp Antiviral Chemotherapy, 1–5 October 1989, Porto Cervo, Italy, (Abstr) p 15Google Scholar
  51. Pelham HR (1986) Speculations on the function of the major heat shock and glucose-regulated proteins. Cell 46:959–961PubMedCrossRefGoogle Scholar
  52. Peluso RW, Lamb RA, Choppin PW (1977) Polypeptide synthesis in simian virus 5-infected cells. J Virol 23:177–187PubMedGoogle Scholar
  53. Peluso RW, Lamb RA, Choppin PW (1978) Infection with paramyxoviruses stimulates synthesis of cellular polypeptides that are also stimulated in cells transformed by Rous sarcoma virus or deprived of glucose. Proc Natl Acad Sci USA 75:6120–6124PubMedCrossRefGoogle Scholar
  54. Ritzi EM, Stylos WA (1976) Prostaglandin production in cultures of BALB/3T3 and SV3T3 mouse fibroblasts. JNCI 56:529–533PubMedGoogle Scholar
  55. Robert A (1981) Prostaglandins and the gastrointestinal tract. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 1407–1434Google Scholar
  56. Roos P, Lindgren JA, Hammarström S (1980) On the mechanism of elevated prostaglandin E2 production in 3T3 fibroblast transformed by polioma virus. Eur J Biochem 108:279–283PubMedCrossRefGoogle Scholar
  57. Russel J, Stow EC, Stow ND, Preston CM (1987) Abnormal forms of the herpes simplex virus immediate early polypeptide Vmw 175 induce the cellular stress response. J Gen Virol 68:2397–2406CrossRefGoogle Scholar
  58. Ruwart J, Rush BD, Friedle NM, Piper RD, Kolaja GJ (1981) Protective effects of 16, 16-dimethyl PGE2 on the liver and kidney. Prostaglandins 21:97–102PubMedCrossRefGoogle Scholar
  59. Samuelsson B (1982) Prostaglandins, thromboxanes and leukotrienes: biochemical pathways. In: Powles TJ, Bochman RS, Honn KV, Ramwell P (eds) Prostaglandins and cancer: First International Conference. Alan R Liss Inc, New York, pp 1–19Google Scholar
  60. Santoro MG (1987) Involvement of protein synthesis in the antiproliferative and the antiviral action of prostaglandins. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo, pp 97–114Google Scholar
  61. Santoro MG, Philpott GW, Jaffe BM (1976) Inhibition of tumor growth in vivo and in vitro by prostaglandin E. Nature (Lond) 263:777–779CrossRefGoogle Scholar
  62. Santoro MG, Benedetto A, Jaffe BM (1980a) The role of prostaglandins in Friend erythroleukemia cell growth and differentiation. In: Rossi GB (ed) Erythropoiesis and differentiation in Friend leukemia cells. Elsevier/North Holland Press, Amsterdam New York, pp 553–562Google Scholar
  63. Santoro MG, Benedetto A, Carruba G, Garaci E, Jaffe BM (1980b) Prostaglandin A compounds as antiviral agents. Science 209:1032–1034PubMedCrossRefGoogle Scholar
  64. Santoro MG, Carruba G, Garaci E, Jaffe BM, Benedetto A (1981) Prostaglandins of the A series inhibit Sendai virus replication in cultured cells. J Gen Virol 53:75–83PubMedCrossRefGoogle Scholar
  65. Santoro MG, Jaffe BM, Garaci E, Esteban M (1982a) Antiviral effect of prostaglandins of A series: inhibition of vaccinia virus replication in cultured cells. J Gen Virol 63:435–440PubMedCrossRefGoogle Scholar
  66. Santoro MG, Jaffe BM, Elia G, Benedetto A (1982b) Prostaglandin Ax induces the synthesis of a new protein in cultured AGMK cells. Biochem Biophys Res Comm 107:1179–1184PubMedCrossRefGoogle Scholar
  67. Santoro MG, Jaffe BM, Esteban M (1983a) Prostaglandin A inhibits the replication of vesicular stomatitis virus: effect on virus glycoprotein. J Gen Virol 64:2797–2801PubMedCrossRefGoogle Scholar
  68. Santoro MG, Benedetto A, Zaniratti S, Garaci E, Jaffe BM (1983b) The relationship between prostaglandins and virus replication. Prostaglandins 25:353–364PubMedCrossRefGoogle Scholar
  69. Santoro MG, Crisari A, Benedetto A, Amici C (1986) Modulation of the growth of a human erythroleukemic cell line (K562) by prostaglandins: antiproliferative action of PGAs. Cancer Res 46:6073–6077PubMedGoogle Scholar
  70. Santoro MG, Fukushima M, Benedetto A, Amici C (1987) PGJ2, a new antiviral prostaglandin: inhibition of Sendai virus replication and alteration of virus protein synthesis. J Gen Virol 68:1153–1158PubMedCrossRefGoogle Scholar
  71. Santoro MG, Favalli C, Mastino A, Jaffe BM, Esteban M, Garaci E (1988) Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus. Arch Virol 99:89–100PubMedCrossRefGoogle Scholar
  72. Santoro MG, Garaci E, Amici C (1989a) Prostaglandins with antiproliferative activity induce the synthesis of a heat shock protein in human cells. Proc Natl Acad Sci USA 86:8407–8411PubMedCrossRefGoogle Scholar
  73. Santoro MG, Amici C, Elia G, Benedetto A, Garaci E (1989b) Inhibition of virus protein glycosylation as the mechanism of the antiviral action of prostaglandin A1 in Sendai virus-infected cells. J Gen Virol 70:789–800PubMedCrossRefGoogle Scholar
  74. Shahabi NA, Chegini N, Wittliff JL (1987) Alterations of MCF-7 human breast cancer after prostaglandins PGA1 and PGF treatment. Exp Cell Biol 55:18–27PubMedGoogle Scholar
  75. Singh MK, Yu J (1984) Accumulation of a heat shock-like protein during differentiation of human erythroid cell line K562. Nature (Lond) 309:631–633CrossRefGoogle Scholar
  76. Theodorakis NG, Zand DJ, Kotzbauer PT, Williams GT, Morimoto RI (1989) Hemin-induced transcriptional activation of the HSP70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress response. Mol Cell Biol 9:3166–3173PubMedGoogle Scholar
  77. Vane JR (1987) Antiinflammatory drugs and the arachidonic acid cascade. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo, pp 12–28Google Scholar
  78. Welch WJ, Suhan JP (1985) Morphological studies of the mammalian stress response: characterization of changes in cytoplasmic organelles, cytoskeleton and nucleoli and appearance of intranuclear active filaments in rat fibroblast after heat shock. J Cell Biol 101:1198–1211PubMedCrossRefGoogle Scholar
  79. Wu BJ, Morimoto RI (1985) Transcription of the human hsp70 gene is induced by serum stimulation. Proc Natl Acad Sci USA 82:6070–6074PubMedCrossRefGoogle Scholar
  80. Wu BJ, Hurst HC, Jones NC, Morimoto RI (1986) The E1A 13S product of adenovirus-5 activates transcription of the cellular human HSP70 gene. Mol Cell Biol 6:2994–2999PubMedGoogle Scholar
  81. Wu BJ, Williams G, Morimoto RI (1987) Detection of three protein binding sites in the serum-regulated promoter of the human gene encoding the 70kDa heat-shock protein. Proc Natl Acad Sci USA 84:2203–2207PubMedCrossRefGoogle Scholar
  82. Yamamoto N, Rahman M, Fukushima M, Maeno K, Nishiyama Y (1989) Involvement of prostaglandin-induced proteins in the inhibition of herpes simplex virus replication. Biochem Biophys Res Commun 158:189–194PubMedCrossRefGoogle Scholar
  83. Yaron M, Yaron I, Caspi D, Smentana O, Eylan E, Zor U (1981) RNA and DNA viral stimulation of prostaglandin E production by human synovial fibroblasts. Arthr Rheuma 24:1582–1586Google Scholar
  84. Yura Y, Terashima K, Iga H, Kondo Y, Yanagawa T, Yoshida H, Hiyashi Y, Sato M (1987) Macromolecular synthesis at the early stage of herpes simplex type 2 (HSV 2) latency in a human neuroblastoma cell line IMR-32: repression of late viral polypeptide synthesis and accumulation of cellular heat-shock proteins. Arch Virol 96:17–28PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • M. Gabriella Santoro
    • 1
    • 2
  • Enrico Garaci
    • 1
  • Carla Amici
    • 1
  1. 1.Department of Experimental MedicineII University of RomeTor VergataItaly
  2. 2.Institute of Experimental MedicineNational Council of ResearchRomeItaly

Personalised recommendations