Experientia

, Volume 50, Issue 11–12, pp 1085–1091 | Cite as

Heat shock response in the central nervous system

  • W. J. Koroshetz
  • J. V. Bonventre
Multi-Author Reviews

Abstract

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.

Key words

Excitotoxicity stroke stress response neuro protection ischemia brain neuron 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ashburner, M., and Bonner, J. J., The induction of gene activity in Drosophila by heat shock. Cell17 (1979) 241–254.PubMedGoogle Scholar
  2. 2.
    Barbe, M. F., Tytell, M., Gower, D. J., and Welch, W. J., Hyperthermia protects against light damage in the rat retina. Science241 (1988) 1817–1820.PubMedGoogle Scholar
  3. 3.
    Beal, M. F., Hyman, B. T., and Koroshetz, W. J., Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative disease? Trends Neurosci.16 (1993) 125–131.PubMedGoogle Scholar
  4. 4.
    Black, M. M., Chestnut, M. H., Pleasure, I. T., and Keen, J. H., Stable clathrin: uncoating protein (hsc70) complexes in intact neurons and their axonal transport. J. Neurosci.11 (1991) 2263–2272.Google Scholar
  5. 5.
    Cheetham, M. E., Biron, J. P., and Anderton, B. H., Human homologues of the bacterial heat-shock protein DNAJ are preferentially expressed in neurons. Biochem. J.284 (1992) 469–476.PubMedGoogle Scholar
  6. 6.
    Chin, D. T., Goff, S. A., Webster, T., Smith, T., and Goldberg, A. L., Sequence of the Ion gene in Escherichia coli. A heat-shock gene which encodes the ATP-dependent protease La. J. biol. Chem.263 (1988) 11718–28.PubMedGoogle Scholar
  7. 7.
    Choi, D. W., Ionic dependence of glutamate neurotoxicity in cortical cell culture. J. neurosci.7 (1987) 379–379.Google Scholar
  8. 8.
    Choi, D. W., Cerebral hypoxia: some new approaches and unanswered questions. J. Neurosci.10 (1990) 2493–2501.PubMedGoogle Scholar
  9. 9.
    Chopp, M., Chen, H., Ho, K., Dereski, K. L., Brown, E., Hetzel, F. W., and Welch, K. M., Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat. Neurology39 (1989) 1396–1398.PubMedGoogle Scholar
  10. 10.
    Csernansky, C. A., Canzoniero, L. M. T., and Choi, D. W., Delayed application of aurintricarboxylic acid reduced glutamate neurotoxicity in culture. Soc. Neurosci. Abstr.19 (1993) 25.Google Scholar
  11. 11.
    Dawson, V. L., Dawson, T. L., London, E. D., Bredt, B. S., and Snyder, S. H., Nitric oxide medates glutamate neurotoxicity in primary cortical cultures. Proc. natl Acad. Sci. USA88 (1991) 6368–6371.PubMedGoogle Scholar
  12. 12.
    DeLuca-Flaherty, C., McKay, D. B., Parham, P., and Hill, B. L., Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis. Cell62 (1990) 875–887.PubMedGoogle Scholar
  13. 13.
    Dwyer, B. E., Nishimura, R. N., and Brown, I. R., Synthesis of the major inducible heat shock protein in rat hippocampus after neonatal hypoxiaischemia. Expl. Neurol.104 (1989) 28–31.Google Scholar
  14. 14.
    Evans, D. P., Corbin, J. R., and Tomasovic, S. P., Effects of calcium buffering on the synthesis of the 26 kDa heat-shock protein family. Radiat. Res.127 (1991) 261–268.PubMedGoogle Scholar
  15. 15.
    Furshpan, E. J., and Potter, D. D., Seizure-like activity and cellular damage in rat hipocampal neurons in cell culture. Neuron3 (1989) 199–207.PubMedGoogle Scholar
  16. 16.
    Hollman, M., and Heinemann, S., Cloned glutamate receptors. A. Rev. Neurosci.17 (1994) 31–108.Google Scholar
  17. 17.
    Johnston, K. N., and Kucey, B. L., Competitive inhibition of hsp70 gene expression causes thermosensitivity. Science242 (1988) 1551–1554.PubMedGoogle Scholar
  18. 18.
    Kang, P. J., Ostermann, J., Shilling, J., Neupert, W., Craig, E. A., and Phanner, N., Requirement for HSP70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature348 (1990) 137–142.PubMedGoogle Scholar
  19. 19.
    Kantengwa, S., Capponi, A. M., Bonventre, J. V., and Polla, B. S., Calcium and the heat-shock response in the human monocytic line U-937. Am. J. Physiol.259 (1990) C77–83.PubMedGoogle Scholar
  20. 20.
    Khan, N. A., and Sotelo, J., Heat shock stress is deleterious to CNS cultured neurons microinjected with anti-HSP70 antibodies. Biol. Cell65 (1989) 199–202.PubMedGoogle Scholar
  21. 21.
    Kinouchi, H., Sharp, F. R., Chan, P. H., Koistinaho, J., Sagar, S. M., and Yoshimoto, T., Induction of c-fos, jumB, c-jun, and hsp70 mRNA in cortex, thalamus, basal ganglia, and hippocampus following middle cerebral artery occlusion. J. Cerebr. Blood Flow Metab.13 (1994) 105–115.Google Scholar
  22. 22.
    Kitagawa, K., Matsumoto, M., Tagaya, T., Hata, R., Ueda, H., Ninobe, M., Handa, N., and Kamada, T., Ischemic tolerance phenomenon found in brain. Brain Res.528 (1990) 21–24.PubMedGoogle Scholar
  23. 23.
    Koroshetz, W. J., and Furshpan, E. J., Seizure-like activity and glutamate receptors in hippocampal neurons in culture. Neurosci. Res.13 (1990) S65-S74.Google Scholar
  24. 24.
    Kozutsumi, Y., Segal, M., Normington, K., Gething, M. J., and Sambrook, J., The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature332 (1988) 462–464.PubMedGoogle Scholar
  25. 25.
    Lafon Cazal, M., Pietri, S., Culcasi, M., and Bockaert, J., NMDA-dependent superoxide production and neurotoxicity. Nature364 (1993) 535–537.PubMedGoogle Scholar
  26. 26.
    Landry, J., Chratien, P., Lambert, H., Hickey, E., and Weber, L. A., Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J. Cell Biol.109 (1989) 7–15.PubMedGoogle Scholar
  27. 27.
    Landry, J., Crete, P., Lamarch, S., and Chretien, P., Activation of Ca2+-dependent processes during heat shock: role in cell thermoresistance. Radiat. Res.113 (1988) 426–436.PubMedGoogle Scholar
  28. 28.
    Lee, K. S., Frank, S., Vanderklish, P., Arai, A., and Lynch, G., Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc. natl. Acad Sci. USA88 (1991) 7233–7237.PubMedGoogle Scholar
  29. 29.
    Leustek, T., Amir-Shapira, D., Toledo, H., Brot, N., and Weissbach, H., Autophosphorylation of 70 kDa heat shock proteins. Cell. molec. Biol.38 (1992) 1–10.Google Scholar
  30. 30.
    Leustek, T., Dalie, B., Amir-Shapira, D., Brot, N., and Weissbach, H., A member of the HSP70 family is localized in mitochondria and resembles Escherichia coli Dnak. Proc. natl Acad. Sci. USA86 (1989) 7805–7808.PubMedGoogle Scholar
  31. 31.
    Lindquist, S., The heat-shock response. A. Rev. Biochem.55 (1986) 1151–1191.Google Scholar
  32. 32.
    Liu, Y., Kato, H., Nakata, N., and Kogure, K., Protection of rat hippocampus against ischemic neuronal damage by pretreatment with sublethal ischemia. Brain Res.586 (1992) 121–124.PubMedGoogle Scholar
  33. 33.
    Lowenstein, D. H., Chan, P. H., and Miles, M. F., The stress protein response in cultured neurons: characterization and avidence for a protective role in excitotoxicity. Neuron7 (1991) 1053–1060.PubMedGoogle Scholar
  34. 34.
    Lowenstein, D. H., Simon, R. P., and Sharp, F. R., The pattern of 72kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus. Brain Res.531 (1990) 173–182.PubMedGoogle Scholar
  35. 35.
    Manning-Krieg, U. C., Scherer, P. E., and Schatz, G., Sequential action of mitochondrial chaperones in protein import into the matrix. EMBO J.10 (1991) 3273–3289.PubMedGoogle Scholar
  36. 36.
    Marini, A. M., Kozuka, M., Lipsky, R. H., and Nowak, T. S., 70-kilodalton heat shock protein induction in cerebellar astrocytes and cerebellar granule cells in vitro: Comparison with immunocytochemical localization after hyperthermia in vivo. J. Neurochem.54 (1990) 1509–1516.PubMedGoogle Scholar
  37. 37.
    Mattson, M. P., Murrain, M., Guthrie, P. B., and Kater, S. B., Fibroblast growth factor and glutamate: opposing actions in the generation and degeneration of hippocampal neuroarchitecture. J. Neurosc.9 (1989) 3728–3740.Google Scholar
  38. 38.
    Miller, E., Raese, J. D., and Morrison-Bogorad, M., Expression of heat shock protein 70 and heat shock cognate messenger RNAs in rat cortex and cerebellum after heat shock or amphetamine treatment. J. Neurochem.56 (1991) 2060–2071.PubMedGoogle Scholar
  39. 39.
    Miyata, Y., and Yahara, I., Cytoplasmic 8 S glucocorticoid receptor binds to actin filaments through the 90-kDa heat shock protein moiety. J. biol. Chem.266 (1991) 8779–8783.PubMedGoogle Scholar
  40. 40.
    Mizzen, L. A., Chang, C., Garrels, J. I., and Welch, W. J., Identification, characterization, and purification of two mammalian stress proteins present in mitochondria, grp75, a member of the hsp70 family and hsp58, a homolog of the bacterial groEL protein. J. biol. Chem.264 (1989) 20664–20675.PubMedGoogle Scholar
  41. 41.
    Monyer, H., Harley, D. M., and Choi, D. W., 21-aminosteroids attenuate excitotoxic neuronal injury in cortical cell cultures. Neuron5 (1990) 121–126.PubMedGoogle Scholar
  42. 42.
    Mosser, D. D., Kotzbaure, P. T., Sarge, K. D., and Morimoto, R. I., In vitro activation of heat-shock transcription factor DNA-binding by calcium and biochemical conditions that affect protein conformation. Proc. natl Acad. Sci. USA87 (1990) 3748–3752.PubMedGoogle Scholar
  43. 43.
    Nowak, T. S., Synthesis of a stress protein following transient ischemia in the gerbil. J. Neurochem.45 (1985) 1635–1641.PubMedGoogle Scholar
  44. 44.
    Nowak, T. S., Bond, U., and Schlesinger, M. J., Heat-shock RNA levels in brain and other tissues after hyperthermia and transient ischemia. J. Neurochem.54 (1990) 451–458.PubMedGoogle Scholar
  45. 45.
    Pelham, H., HSP70 accelerates the recovery of nucleolar morphology after heat shock. EMBO J.3 (1984) 3095–3100.PubMedGoogle Scholar
  46. 46.
    Pelham, H., Hpeculation on the function of the major heat shock and glucose-regulated proteins. Cell46 (1986) 959–961.PubMedGoogle Scholar
  47. 47.
    Picard, D., Khursheed, B., Garabedian, M., Fortin, M., Lindquist, S., and Yamamoto, K., Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature348 (1990) 166–168.PubMedGoogle Scholar
  48. 48.
    Price, B. D., and Calderwood, S. K., Calcium is essential for multistep activation of the heat shock factor in permeabilized cells. Molec. cell Biol.11 (1991) 3365–3368.PubMedGoogle Scholar
  49. 49.
    Riabowol, K. T., Mizzen, L. A., and Welch, W. J., Heat shock is lethal to fibroblasts microinjected with antibodies against HSP70. Science242 (1988) 433–436.PubMedGoogle Scholar
  50. 50.
    Rordorf, G., Koroshetz, W. J., and Bonventre, J. V., Heat shock protects cultured neurons from glutamate toxicity. Neuron7 (1991) 1043–1051.PubMedGoogle Scholar
  51. 51.
    Rose, K., Bruno, R., Oliker, R., and Choi, D. W., Nordihydroguairetic acid attenuates slow excitatory amino acid-induced neuronal degeneration in cortical cultures. Soc. Neurosci. Abstr.16 (1990) 288.Google Scholar
  52. 52.
    Rosenberg, P. A., Amin, S., and Leitner, M., Glutamate uptake disguises neurotoxic potency of glutamate agonists in dissociated cell culture. J. Neurosci.12 (1992) 56–61.PubMedGoogle Scholar
  53. 53.
    Rothman, S. M., Thruston, J. H., and Hauhart, R. E., Delayed neurotoxicity of excitatory amino acids in vitro. Neuroscience22 (1987) 471–480.PubMedGoogle Scholar
  54. 54.
    Sharp, F. R., Lowenstein, D., Simon, R. P., and Hisanga, K., Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction. J. Cerebr. Blood Flow Metab.11 (1991) 621–627.Google Scholar
  55. 55.
    Sherman, M. Y. U., and Goldberg, A. L., Involvement of the chaperonin dnaK in the rapid degraduation of a mutant protein in Escherichia coli. EMBO J11 (1992) 71–77.PubMedGoogle Scholar
  56. 56.
    Shimosaka, S., So, Y. T., and Simon, R. P., Distribution of HSP72 induction and neuronal death following limbic seizures. Neurosci. Lett138 (1992) 202–206.PubMedGoogle Scholar
  57. 57.
    Siman, R., and Noszek, J. C., Excitatory amino acids activate calpain I and induce structural protein breakdown in vivo. Neuron1 (1988) 279–287.PubMedGoogle Scholar
  58. 58.
    Simon, R., Cho, J., Gwinn, R., and Lowenstein, D., The temporal profile of 72kd heat shock protein expression following global ischemia. J. Neurosci.11 (1991) 881–889.PubMedGoogle Scholar
  59. 59.
    Simon, R. P., Niiro, M., and Gwinn, R., Prior ischemic stress protects against experimental stroke. Neurosci. Lett.163 (1993) 135–137.PubMedGoogle Scholar
  60. 60.
    Sloviter, R. S., and Lowenstein, D. H., Heat shock expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress. J. Neurosci.12 (1992) 3004–3009.PubMedGoogle Scholar
  61. 61.
    Sorger, P. K., and Pelham, H. R., Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell54 (1988) 855–864.PubMedGoogle Scholar
  62. 62.
    Stevenson, M. A., and Calderwood, S. K., Members of the 70kDa heat shock protein family contain a highly conserved calmodulin-binding domain. Molec. cell. Biol.10 (1990) 1234–1238.PubMedGoogle Scholar
  63. 63.
    Ting, L. P., Tu, C. L., and Chou, C. K., Insulin-induced expression of human heat-shock protein gene hsp70. J. biol. Chem.264 (1989) 3404–3408.PubMedGoogle Scholar
  64. 64.
    Tymianski, M., Wallace, M. C., Spigleman, I., Uno, M., Carlen, P. L., Tator, C. H., and Charlton, M. P., Cell-permeant Ca2+ chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo. Neuron11 (1993) 221–235.PubMedGoogle Scholar
  65. 65.
    Tytell, M., Greenberg, S., and Lasek, R., Heat shock-like protein is transferred from glia to axon. Brain Res.363 (1986) 161–164.PubMedGoogle Scholar
  66. 66.
    Vass, K., Berger, M. L., Nowak, T. S., Welch, W. J., and Lassman, H., Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat. Neurosci. Lett.100 (1989) 259–264.PubMedGoogle Scholar
  67. 67.
    Wang, Z. H., Vidair, C. A., and Dewey, W. C., Maintenance of intracellular free Ca++ homeostasis following lethalheat shock. Radiat. Res.128 (1991) 104–107.PubMedGoogle Scholar
  68. 68.
    Welch, W. J., and Suhan, J. P., Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J. Cell Biol.103 (1986) 2035–2052.PubMedGoogle Scholar
  69. 69.
    Wertheimer, E. S., Cerasi, E., and Ben-Neriah, Y., The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins. Proc. natl Acad. Sci. USA88 (1991) 2525–2529.PubMedGoogle Scholar
  70. 70.
    Whatley, S. A., Leung, T., Hall, C., and Lin, L., The brain 68-kilodalton microtubule-associated protein is a cognate form of the 70-kilodalton mammalian heat-shock protein and is present as a specific isoform in synaptosomal membranes. J. Neurochem.47 (1986) 1576–1583.PubMedGoogle Scholar
  71. 71.
    Wu, C., Wilson, S., Walker, B., Dawid, I., Paisley, T., Zimarino, V., and Ueda, H., Purification and properties of drosophilia heat shock activator protein. Science238 (1987) 1247–1253.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel 1994

Authors and Affiliations

  • W. J. Koroshetz
    • 1
  • J. V. Bonventre
    • 2
  1. 1.Neurology and Medical Service, Massachusetts General HospitalHarvard Medical School, Kennedy 915, Massachusetts General HospitalBostonUSA
  2. 2.Medical Service, Massachusetts General HospitalHarvard Medical School, Suite 4002, Massachusetts General Hospital EastCharlestownUSA

Personalised recommendations