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Stress (heat shock) proteins and rheumatic disease

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Summary

Protein synthesis in all cells is readily interrupted by environmental stresses such as hyperthermia. However, stressed cells also have mechanisms which, even under conditions where normal protein synthesis is completely inhibited, allow them to synthesise a group of highly conserved proteins — the so-called heat shock proteins (HSP). Some of these proteins are now known to facilitate the recovery of normal RNA processing and protein synthesis after exposure to hyperthermia and to protect the cell against further damage. They also play an important role in the synthesis and transport of normal proteins in unstressed cells, and perhaps also the export from cells of abnormal proteins of host or viral origin. Synthesis of HSP is also triggered by exposure to stresses other than hyperthermia, for example heavy metals (e.g. gold complexes), thiol-reactive chemicals, near UV radiation, viruses, oxyradicals and certain cytokines. Furthermore, there are also a number of proteins which are induced by these physicochemical stresses but not by heat; for this reason “stress protein” will be used as a general term to describe both HSP and related, physicochemically-induced, proteins. The cysteine-rich metallothioneins, which behave in some respects as stress proteins, will not be included in this review. Because many of the factors which stimulate stress protein induction occur during inflammatory and immune responses, there has been increasing interest in the possible role of stress proteins in inflammatory disease such as arthritis. The purpose of this article is to review the basic biochemical mechanisms involved in the induction of stress proteins and offer some speculations on their potential role in rheumatic disease.

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References

  1. Ritossa F (1962) A new puffing pattern induced by heat shock and DNP in Drosophila. Experientia 18:571–573

    Google Scholar 

  2. Tissieres A, Mitchell HK, Tracey UM (1974) Protein synthesis in salivary glands of D. melanogaster. Relation to chromosome puffs. J Mol Biol 84:389–398

    Google Scholar 

  3. Yost HJ, Lindquist S (1986) RNA splicing is interrupted by heat shock and is rescued by HSP synthesis. Cell 45:185–193

    Google Scholar 

  4. Spradling A, Penman S, Pardue ML (1975) Analysis of Drosophila mRNA by in situ hybridisation: sequences transcribed in normal and heat shocked cultured cells. Cell 4:395–404

    Google Scholar 

  5. Lindquist S (1981) Regulation of protein synthesis during heat shock. Nature 293:311–314

    Google Scholar 

  6. Storti RV, Scott MP, Rich A, Pardue ML (1980) Translational control of protein synthesis in response to heat shock in D. melanogaster cells. Cell 22:825–834

    Google Scholar 

  7. McGarry TJ, Lindquist S (1985) The preferential translation of Drosophila hsp 70 mRNA requires sequences in the untranslated leader. Cell 42:903–911

    Google Scholar 

  8. Hunt C, Morimoto RI (1985) Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci USA 82:6455–6459

    Google Scholar 

  9. Pelham HRB (1986) Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell 46:959–961

    Google Scholar 

  10. Polla BS (1988) A role for heat shock proteins in inflammation? Immunology Today 9:134–137

    Google Scholar 

  11. Kasambalides EJ, Lanks KW (1983) Dexamethasone can modulate glucose-regulated and heat shock protein synthesis. J Cell Physiol 114:93–98

    Google Scholar 

  12. Ramachandran C, Catelli MG, Schneider W, Shyamala G (1988) Estrogenic regulation of uterine 90-kilodalton heat shock protein. Endocrinology 123:956–961

    Google Scholar 

  13. Baez M, Sargan DR, Elbrecht A, Kulomaa MS, Zarucki-Schulz T, Tsai M-J, O'Malley BW (1987) Steroid hormone regulation of the gene encoding the chicken heat shock protein hsp 108. J Biol Chem 262:6582–6588

    Google Scholar 

  14. Caltabiano MM, Koestler TP, Poste G, Greig RG (1986) Induction of 32- and 34-kDa proteins by sodium arsenite, heavy metals, and thiol-reactive agents. J Biol Chem 261:13381–13386

    Google Scholar 

  15. Keyse SM, Tyrell M (1987) Both near ultraviolet radiation and the oxidising agent hydrogen peroxide induce a 32kDa stress protein in normal human skin fibroblasts. J Biol Chem 262:14821–14825

    Google Scholar 

  16. Velazquez JM, DiDomenico BJ, Lindquist S (1980) Intracellular localisation of heat shock proteins in Drosophila. Cell 20:679–689

    Google Scholar 

  17. Velazquez JM, Lindquist S (1984) hsp70: nuclear function during environmental stress and cytoplasmic storage during recovery. Cell 36:655–662

    Google Scholar 

  18. Welch WJ, Suhan JP (1986) Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol 103:2035–2052

    Google Scholar 

  19. Lewis MJ, Pelham HRB (1985) Involvement of ATP in the nuclear and nucleolar functions of the 70 kD heat shock protein. EMBO J 4:3137–3143

    Google Scholar 

  20. Laszlo A (1988) The relationship of heat shock proteins, thermotolerance and protein synthesis. Exp Cell Res 178:401–414

    Google Scholar 

  21. Pelham HRB (1984) HSP70 accelerates the recovery of nucleolar morphology after heat shock. EMBO J 3:3095–3100

    Google Scholar 

  22. Pelham HRB (1988) Heat shock proteins — coming in from the cold. Nature 332:776–777

    Google Scholar 

  23. Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332:800–805

    Google Scholar 

  24. Chirico WJ, Waters MG, Blobel G (1988) 70K heat shock related proteins stimulate protein translocation into microsomes. Nature 332:805–810

    Google Scholar 

  25. White E, Spector D, Welch W (1988) Differential distribution of the adenovirus E1A proteins and colocalisation of E1A with the 70-kilodalton cellular heat shock protein in infected cells. J Virol 62:4153–4166

    Google Scholar 

  26. Khanadjian EW, Turlen H (1983) Simian virus 40 and polyoma virus induce synthesis of heat shock proteins in permissive cells. Mol Cell Biol 3:1–8

    Google Scholar 

  27. La Thangue NB, Latchman DS (1988) A cellular protein related to heat shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells. Exp Cell Res 178:169–179

    Google Scholar 

  28. Provost TT, Reichlin M (1988) Immunopathologic studies of cutaneous lupus erythematosus. J Clin Immunol 8:223–233

    Google Scholar 

  29. Bole DG, Hendershot LM, Kearney JF (1986) Post-translational association of immunoglobulin heavy chain binding protein with nascent heavy chains in nonsecreting and secreting hybridomas. J Cell Biol 102:1558–1566

    Google Scholar 

  30. Munro S, Pelham HR (1986) An HSP70-like protein in the ER: identity with the 78kD glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46:291–300

    Google Scholar 

  31. Kozutsumi YY, Segal M, Normington K, Gething M-J, Sambrook J (1988) The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332:462–464

    Google Scholar 

  32. Catelli MG, Binart N, Jung-Testas I, Renoir JM, Baulieu EE, Feramisco JR, Welch WJ (1985) The common 90 kD protein component of non-transformed “8S” steroid receptors is a heat shock protein. EMBO J 4:3131–3136

    Google Scholar 

  33. Schuh S, Yonomoto W, Brugge J, Bauer VJ, Rich RM, Sullivan WP, Toft D (1985) A 90 000-dalton binding protein comon to both steroid receptors and the Rous sarcoma virus transforming protein, pp 60v-ser. J Biol Chem 260:14292–14296

    Google Scholar 

  34. Baulieu EE (1987) Steroid hormone antagonists at the receptor level: a role for heat shock protein MW 90 000 (hsp90). J Cell Biochem 35:161–174

    Google Scholar 

  35. Pratt WB (1987) Transformation of glucocorticoid and progesterone receptors to the DNA-binding state. J Cell Biochem 35:51–68

    Google Scholar 

  36. Danielsen M, Northrop J, Ringold GM (1986) The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild-type and mutant receptor proteins. EMBO J 5:2513–2522

    Google Scholar 

  37. Sabbah M, Redeuilh G, Secco C, Baulieu E-E (1987) The binding activity of estrogen receptor to DNA and heat shock protein (Mr 90 000) is dependent on receptor bound metal. J Biol Chem 262:8631–8635

    Google Scholar 

  38. Southgate R, Ayme A, Voellmy R (1983) Nucleotide sequence analysis of the Drosophila small heat shock gene cluster at locus 67B. J Mol Biol 165:35–37

    Google Scholar 

  39. Keyse SM, Tyrell RM (1989) Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide and sodium arsenite. Proc Natl Acad Sci USA 86:99–103

    Google Scholar 

  40. Muller RM, Taguchi H, Shibahara S (1987) Nucleotide sequence and organisation of the rat heme oxygenase gene. J Biol Chem 262:6795–6802

    Google Scholar 

  41. Yoshida T, Biro P, Cohen T, Muller RM, Shibahara S (1988) Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem 171:457–461

    Google Scholar 

  42. Yoshida T, Kikuchi G (1978) Purification and properties of heme oxygenase from pig spleen microsomes. J Biol Chem 253:4224–4229

    Google Scholar 

  43. Hass MA, Massaro D (1988) Regulation of the synthesis of superoxide dismutases in rat lungs during oxidant and hyperthermic stresses. J Biol Chem 263:776–781

    Google Scholar 

  44. Duff GW, Durum SK (1983) The pyrogenic and mitogenic actions of interleukin-1 are related. Nature 304:449–451

    Google Scholar 

  45. Kluger MJ (1986) Is fever beneficial? Yale J Biol Med 59:89–95

    Google Scholar 

  46. Granelli-Piperno A, Andrus L, Steinman RM (1986) Lymphokine and nonlymphokine mRNA levels in stimulated human T cells. J Exp Med 163:922–937

    Google Scholar 

  47. Polla BS, Healy AM, Wojno WC, Krane SM (1987) Hormone 1 alpha, 25 dihydroxyvitamin D3 modulates heat shock response in monocytes. Am J Physiol 252 (6 Pt1):C640-C649

    Google Scholar 

  48. Spitz DR, Dewey WC, Li GC (1987) Hydrogen peroxide or heat shock induces resistance to hydrogen peroxide in Chinese hampster fibroblasts. J Cell Physiol 131:364–373

    Google Scholar 

  49. Polla BS, Healey AM, Wojno WC, Krane SM (1986) Abstract. J Bone Min Res 1:422

    Google Scholar 

  50. Polla BS, Healey AM, Amento EP, Krane SM (1986) 1,25 dihydroxyvitamin D3 maintains adherence of human monocytes and protects them from thermal injury. J Clin Invest 77:1332–1339

    Google Scholar 

  51. Kubo T, Towle CA, Mankin HJ, Treadwell BV (1985) Stress-induced proteins in chondrocytes from patients with osteoarthritis. Arthritis Rheum 28:1140–1145

    Google Scholar 

  52. McLean IL, Winrow VR, Mapp PI, Cherrie AH, Archer JR, Blake DR (1988) Letter — synovial fluid T cells and 65 kD heat shock protein. Lancet II p:856–857

    Google Scholar 

  53. Res PCM, Schaar CG, Breedveld FC, van Eden W, van Embden JDA, Cohen IR, de Vries RRP (1988) Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis. Lancet II:478–480

    Google Scholar 

  54. Gaston JSH, Life PF, Bailey L, Bacon PA (1988) Letter — synovial fluid T cells and 65 kD heat shock protein. Lancet II:856

    Google Scholar 

  55. Pardue ML (1988) The heat shock response in biology and human disease: a meeting review. Genes Dev 2:783–785

    Google Scholar 

  56. Minota S, Cameron B, Welch WJ, Winfield JB (1988) Autoantibodies to the constitutive 73 kD member of the hsp70 family of heat shock proteins in systemic lupus erythematosus. J Exp Med 168:1475–1480

    Google Scholar 

  57. Caltabiano MM, Kiestler TP, Poste G, Greig RG (1986) Induction of mammalian stress proteins by a triethylphosphine gold compound used in therapy of rheumatoid arthritis. Biochem Biophys Res Commun 138:1074–1080

    Google Scholar 

  58. Smith MD, Smith A, O'Donnell J, Ahern M, Roberts-Thomson PJ (1989) Impaired delayed type hypersensitivity in rheumatoid arthritis reversed by chrysotherapy. Ann Rheum Dis 48:108–113

    Google Scholar 

  59. Hurst NP, Bell AL, Nuki G (1986) Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes. Ann Rheum Dis 45:37

    Google Scholar 

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  1. Rheumatic Diseases Unit, Northern General Hospital, Ferry Road, EH5 2DQ, Edinburgh, Scotland

    N. P. Hurst

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Hurst, N.P. Stress (heat shock) proteins and rheumatic disease. Rheumatol Int 9, 271–276 (1990). https://doi.org/10.1007/BF00541323

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