Skip to main content
SpringerLink
Log in

Molecular chaperones and disease

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Molecular chaperones are intracellular proteinfolding proteins which form part of an ancient cellular response to stress called the heat shock response. They have been the focus for attention during the last decade because of the discovery of their vital role in cell functioning. In very recent years additional roles for these ‘topologically-active’ proteins in the process of tissue pathology and its treatment have been indicated and are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ritossa F. A new puffing pattern induced by temperature and DNP inDrosophila. Experientia 1962;18:571–3.

    Google Scholar 

  2. Bakau B. Regulation of theEscherichia coli heat shock response. Mol Microbiol 1993;9:671–80.

    Google Scholar 

  3. Lindquist S. The heat shock response. Ann Rev Biochem 1986;55:1151–91.

    Google Scholar 

  4. Laskey RA, Honda BM, Mills AD, Finch JT. Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature 1978;275:416–20.

    Google Scholar 

  5. Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopolous GC, et al. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 1988;333:330–4.

    Google Scholar 

  6. Minowanda G, Welch WJ. Clinical implications of the stress response. J Clin Invest 1995;95:3–12.

    Google Scholar 

  7. Herschlag D. RNA chaperones and the RNA folding problem [review]. J Biol Chem 1995;270:20871–4.

    Google Scholar 

  8. Craig E, Jacobsen K. Mutations of the heat-inducible 70 kilodalton genes of yeast confer temperature sensitive growth. Cell 1984;38:841–9.

    Google Scholar 

  9. Riabowo KT, Mizzen LA, Welch WJ. Heat shock is lethal to fibroblasts microinjected with antibodies against hsp 70. Science 1988;242:433–6.

    Google Scholar 

  10. Young DB, Mehlert A, Smith DF, Stress proteins and infectious diseases. In: Morimoto RI, Tissieres A, Geogopoulos C, editors. Stress Proteins in Biology and Medicine. Cold Spring Harbor: Cold Spring Harbor Press, 1990:131–65.

    Google Scholar 

  11. Young DB. Heat shock proteins: immunity and autoimmunity. Curr Opin Immunol 1992;4:396–400.

    Google Scholar 

  12. Blachere NE, Udono H, Janetski S, Li Z, Heike M, Srivastava PK. Heat shock protein vaccines against cancer. J Immunother 1993;14:352–6.

    Google Scholar 

  13. Udono H, Srivastava PK. Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp 70. J Immunol 1994;152:5398–403.

    Google Scholar 

  14. Suto R, Srivastava PK. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 1995;269:1585–8.

    Google Scholar 

  15. Edgington SM. Therapeutic application of heat shock proteins. Biotechnology 1995;13:1442–4.

    Google Scholar 

  16. Lukacs KV, Lowrie DB, Stokes RW, Colston MJ. Tumour cells transfected with a bacterial heat shock gene lose tumorigenicity and induce protection against tumours. J Exp Med 1993;178:343–8.

    Google Scholar 

  17. Elias D, markovits D, Reshef T, Van der Zee R, Cohen IR. Induction and therapy of autoimmune diabetes in the nonobese diabetic (NOD/Lt) mouse by a 65 kDa heat shock protein. Proc Natl Acad Sci USA 1990;87:1576–80.

    Google Scholar 

  18. van Eden W, Thole JE, Van der Zee R, Noordzij A, van Embden JD, Hensen EJ, et al. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 1988;331:171–3.

    Google Scholar 

  19. Thompson SJ, Hitsumoto Y, Ghoraishian M, van der Zee R, Elson CJ. Cellular and humoral reactivity pattern to the mycobacterial heat shock protein hsp 65 in pristane-induced arthritis-susceptible and hsp 65-protected DBA/1 mice. Autoimmunity 1991;11:89–95.

    Google Scholar 

  20. Anderton SM, van der Zee R, Noordzij A, van Eden W. Differential mycobacterial 65-kDa heat shock protein T cell epitope recognition after adjuvant arthritis-inducing or protective immunization protocols. J Immunol 1994;152:3656–64.

    Google Scholar 

  21. Cavanagh AC, Morton H. The purification of early pregnancy factor to homogeneity from human platelets and identification as chaperonin 10. Eur J Biochem 1994;222:551–60.

    Google Scholar 

  22. Welch WJ. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 1992;72:1063–81.

    Google Scholar 

  23. DeNagel DC, Pierce SK. Heat shock proteins in immune responses. Crit Rev Immunol 1993;13:71–81.

    Google Scholar 

  24. Coates ARM. Immunological aspects of chaperonins. In: Ellis RJ, editor. The chaperonins. Academic Press, 1996. In press.

  25. Sargent CA, Dunham I, Trowsdale J, Campbell RD. Human major histocompatibility complex contains genes for the major heat shock protein hsp 70. Proc Natl Acad Sci USA 1989;86: 1968–72.

    Google Scholar 

  26. Young D, Roman E, Moreno C, O'Brien R, Born W. Molecular chaperones and the immune response. In: Ellis RJ, Laskey RA, Lorimer GH, editors. Molecular chaperones. Chapman and Hall, 1993;107–12.

  27. Delcayre CJ, Samuel L, Marotte F, Best-Belpomme JJ, Mercadier, Rapoport L. Synthesis of stress proteins in rat cardiac myocytes 2–4 days after imposition of hemodynamic overload. J Clin Invest 1988;82:460–8.

    Google Scholar 

  28. Donnelly TJ, Sievers RE, Vissern FLJ, Welch WJ, Wolfe CL. Heat shock protein induction in rat hearts: a role for improved myocardial salvage after ischaemia and reperfusion. Circulation 1992;85:769–78.

    Google Scholar 

  29. Currie RW, Tanguay RM, Kingma JG. 1993. Heat shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts. Circulation 1993;87:963–71.

    Google Scholar 

  30. Marber MS, Mestril R, Shun-Hua Chi M, Sayen R, Yellon DM, Dillman WH. 1995. Overexpression of the rat inducible 70-kDa stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest 95:1446–56.

    Google Scholar 

  31. Koenig WJ, Lohner RA, Perdrizet GA, Lohner ME, Schweitzer RT, Lewis VL. Improving acute skin-flap survival through stress-conditioning using heat shock and recovery. Plast Reconstr Surg 1992;90:659–64.

    Google Scholar 

  32. Horwitz J. Alpha crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 1992;89:10449–53.

    Google Scholar 

  33. Schaurte JA, Gafni A. Photodegradation of tryptophan residues and attenuation of molecular chaperone activity of alpha-crystallin are correlated. Biochem Biophys Res Commun 1995;212:900–5.

    Google Scholar 

  34. Jurivich DA, Sistonen L, Kroes RA, Morimoto RI. Effect of sodium salicylate on the human heat shock response. Science 1992;255:1243–5.

    Google Scholar 

  35. Lee BS, Chen J, Angelidis C, Jurivich DA, Morimoto RI. Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage. Proc Natl Acad Sci USA 1995;92:7207–11.

    Google Scholar 

  36. Nadler SG, Tepper MA, Schacter B, Mazzucco CE. Interaction of the immunosuppressant deoxyspergualin with a member of the hsp70 family of heat shock proteins. Science 1992;258:484–6.

    Google Scholar 

  37. Tepper MA, Nadler SG, Esselstyn JM, Sterbenz KG. Deoxyspergualin inhibits κ light chain expression in 70Z/3 pre-B cells by blocking lipopolysaccharide-induced NfκB activation. J Immunol 1995;155:2427–36.

    Google Scholar 

  38. Wynn RM, Davie JR, Cox RP, Chuang DT. Molecular chaperones: heat shock proteins, foldases, and matchmakers. J Lab Clin Med 1994;124:31–6.

    Google Scholar 

  39. Schultz DR, Arnold PI. Heat shock (stress) proteins and autoimmunity in rheumatic diseases. Semin Arthr Rheum 1993;22:357–74.

    Google Scholar 

  40. Ma J, Yee A, Brewer HB, Das S, Potter H. Amyloid-associated proteins α-1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 1994;372:92–4.

    Google Scholar 

  41. Liautard JP. A hypothesis on the aetiology of Alzheimer's disease: description of a model involving a misfolded chaperone. Med Hypoth 1994;43:372–80.

    Google Scholar 

  42. Ellis RJ. The general concept of molecular chaperones.In: Ellis RJ, Laskey RA, Lorimer GH, editors. Molecular Chaperones. London: Chapman and Hall: 1993: 1–5.

    Google Scholar 

  43. Martinus RD, Ryan MT, Naylor DJ, Herd SM, Hoogenraad NJ, Hoj PB. The role of chaperones in the biogenesis and maintenance of the mitochondrion. FASEB J 1995;9:371–8.

    Google Scholar 

  44. Agsteribbe E, Huckriede A, Veenhuis M, Ruiters MJH, Niezen-Koning KE, Skjedal K, et al. A fatal, systemic mitochondrial disease with decreased mitochondrial enzyme activities, abnormal ultrastructure of the mitochondria and deficiency of heat shock protein 60. Biochem Biophys Res Commun 1993;193:146–54.

    Google Scholar 

  45. Alder GM, Austen BM, Bashford CL, Mehlert A, Pasternak CA. Heat shock proteins induce pores in membranes. Bioscience Reports 1990;10:509–18.

    Google Scholar 

  46. Henderson B, Wilson M. Modulins: A new class of cytokine-inducing, pro-inflammatory bacterial virulence factor. Inflamm Res 1995;44:187–97.

    Google Scholar 

  47. Beagley KW, Fujihasha K, Black CA, Lagoo AS, Yamamoto M, McGhee JR, et al. TheMycobacterium tuberculosis 71 kDa heat shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes. Eur J Immunol 1993;23:2049–52.

    Google Scholar 

  48. Friedland JS, Shattock R, Remick DG, Griffin GE. Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells. Clin Exp Immunol 1993;91:58–62.

    Google Scholar 

  49. Retzlaff C, Yamomoto Y, Hoffman PS, Friedman H, Klein TW. Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. Infect Immun 1994;62:5689–93.

    Google Scholar 

  50. Kirby AC, Meghji S, Nair SP, White P, Reddi K, Nishihara T, et al. The potent bone-resorbing mediator ofActinobacillus actinomycetemcomitans is homologous to the molecular chaperone groEL. J Clin Invest 1995;1185–94.

  51. Nair SP, Meghji S, Wilson M, Miller AD, Henderson B. Heat shock proteins stimulate bone resorption. J Bone Miner Res. In press.

Download references

Author information

Authors and Affiliations

  1. Maxillofacial Surgery Research Unit, Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Gray's Inn Road, WC1X 8LD, London, UK

    B. Henderson & S. P. Nair

  2. Division of Molecular Microbiology, Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, Cranmer Terrace, SW17 ORE, London, UK

    A. R. M. Coates

Authors
  1. B. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. P. Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. R. M. Coates
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

accepted by R. Pettipher

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henderson, B., Nair, S.P. & Coates, A.R.M. Molecular chaperones and disease. Inflamm Res 45, 155–158 (1996). https://doi.org/10.1007/BF02285154

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02285154

Key words

Search

Navigation