Skip to main content
Log in

Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: Relevance to neurodegenerative disease

  • Original Articles
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Summary

We studied heat shock protein (HSP) synthesis by cultured human neuroblastoma cells in response to either hyperthermia or high levels of superoxide anion (oxygen free radical). Both treatment modalities resulted in induced synthesis of the same major HSP species with an additive effect on the latter and on cell growth inhibition upon combined treatments. Exposure to superoxide anion in the presence of the free radical scavening enzymes, superoxide dismutase and catalase improved cell survival and prevented HSP induction. These findings suggest a common mechanism by which various forms of injury, such as hyperthermia, cause HSP induction, that is, via oxidative stress or increased production of oxygen free radicals. Increased expression of some HSPs has been detected in association with the pathological lesions that characterize some neurodegenerative diseases such as the neurofibrillary tangles of Alzheimer's disease. This, in turn, suggests that chronic oxidative stress may play a role in the pathogenesis of these disorders.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ananthan J, Goldberg A, Voellmy R (1986) Abnormal proteins serve as eukaryotic stress signal and trigger the activation of heat shock genes. Science 232:522–525

    Google Scholar 

  • Ashburner M, Bonner J (1979) The induction of gene activity inDrosophila by heat shock. Cell 17:241–254

    Google Scholar 

  • Becker J, Mezger V, Courgeon AM, Best-Belpomme M (1990) Hydrogen peroxide activates immediate binding of aDrosophila factor to DNA heat-shock regulatory element in vivo and in vitro. Eur J Biochem 189:553–558

    Google Scholar 

  • Beckman RP, Mizzen LA, Welch WJ (1989) Interaction of hsp70 with newly synthesized proteins: implications for protein folding and assembly. Science 248:850–854

    Google Scholar 

  • Burdon RH, Gill V, Rice-Evans C (1987) Oxidative stress and heat shock protein induction in human cells. Free Radic Res Commun 3:129–139

    Google Scholar 

  • Cajone F, Bernell-Zazzera A (1988) Oxidative stress induces a subset of heat shock proteins in rat hepatocytes and MH1C1 cells. Chem Biol Interact 65:235–246

    Google Scholar 

  • Compton J, McCarthy B (1978) Induction of theDrosophila heat shock response in isolated polytene nuclei. Cell 14:191–201

    Google Scholar 

  • Flohe L, Otting F (1984) Superoxide dismutase assays. Methods Enzymol 105:93–104

    Google Scholar 

  • Frank L, Wood D, Roberts R (1987) Effect of diethyldithiocarbamate on oxygen toxicity and lung enzyme activity in immature and adult rats. Biochem Pharmacol 27:251–254

    Google Scholar 

  • Freeman B, Crapo J (1982) Free radicals and tissue injury. Lab Invest 47:412–426

    Google Scholar 

  • Glass J, Dewitt R, Cress A (1985) Rapid loss of stress fibers in Chinese hamster ovary cells after hyperthermia. Cancer Res 45:258–262

    Google Scholar 

  • Goff S, Voellmy R, Goldberg A (1988) Protein breakdown and the heat shock response. In: Rechsteiner M (ed) Ubiquitin. Plenum Press, New York, pp 207–216

    Google Scholar 

  • Hamos J, Oblas B, Pulaski-Salo D, et al (1991) Expression of heat shock proteins in Alzheimer's disease. Neurology 41:345–350

    Google Scholar 

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

    Google Scholar 

  • Kelley P, Schlesinger M (1978) The effect of aminoacid analogues and heat shock on gene expression in chicken embryo fibroblasts. Cell 15:1277–1286

    Google Scholar 

  • Keyse S, Tyrrell R (1987) Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts. J Biol Chem 262:14821–14825

    Google Scholar 

  • Keyser J, Ebinger G, Vauquelin G (1990) D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer's disease. Arch Neurol 47:761–763

    Google Scholar 

  • Konnings A, Ruifrok A (1985) Role of membrane lipids and membrane fluidity in thermosensitivity and thermotolerance of mammalian cells. Radiat Res 102:86–98

    Google Scholar 

  • Landry J, Chretien P, Lambert H et al (1989) Heat shock resistance conferred by expression of the human HSP 27 gene in rodent cells. J Cell Biol 109:7–15

    Google Scholar 

  • Langstrom NS, Anderson JP, Lindroos HG, et al (1989) Alzheimer's disease-associated reduction of polysomal mRNA translation. Mol Brain Res 5:259–269

    Google Scholar 

  • Levinson W, Opperman H, Jackson J (1980) Transition series metals and sulfhydryl reagents induce the synthesis of four proteins in eukaryotic cells. Biochem Biophys Acta 60:170–180

    Google Scholar 

  • Lindquist S, Craig EA (1988) The heat shock proteins. Ann Rev Genet 22:631–677

    Google Scholar 

  • Loven D, Leeper D, Oberley L (1985) Superoxide dismutase levels in Chinese hamster ovary cells and ovarian carcinoma cells after hyperthermia or exposure to cycloheximide. Cancer Res 45:3029–3033

    Google Scholar 

  • Lowe J, Blanchard A, Morrell K et al (1988) Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibers in cerebellar astrocytomas and cytoplasmic bodies in muscle and Mallory bodies in alcoholic liver disease. J Pathol 155:9–15

    Google Scholar 

  • Lu AY, Lin Z, Choi HS, et al (1989) Attenuated induction of heat shock gene expression in aging diploid fibroblasts. J Biol Chem 264:12037–12045

    Google Scholar 

  • Mayer RJ, Arnold J, Laszlo L, et al (1991) Ubiquitin in health and disease, Biochim Biophys Acta 1089:141–157

    Google Scholar 

  • Mori H, Kondo J, Ihara I (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235:1641–1644

    Google Scholar 

  • Muller-Hill B, Beyreuther K (1989) Molecular biology of Alzheimer's disease. Annu Rev Neurosci 58:287–307

    Google Scholar 

  • Oliver CN, Ahn BW (1987) Age-related changes in oxidized proteins. J Biol Chem 262:5488–5491

    Google Scholar 

  • Omar R, Lanks K (1984) Heat shock protein synthesis and cell survival in clones of normal and SV40-transformed mouse embryo cells. Cancer Res 44:3967–3982

    Google Scholar 

  • Omar R, Pappolla M (1990) Aluminum toxicity potentiates the effect of oxidative stress: relevance to Alzheimer's disease (abstract). International Academy of Pathology OP36. XVIII Congress of the IAP, Buenos Aires, Argentina

  • Omar R, Yano S, Kikkawa Y (1987) Antioxidant enzyme and survival of normal and SV40 transformed mouse embryo cells after hyperthermia. Cancer Res 47:3473–3476

    Google Scholar 

  • Omar R, Pappolla M, Saran B (1990a) Immunocytochemical detection of the 70 Kd heat shock protein in alcoholic liver disease. Arch Pathol Lab Med 114:589–593

    Google Scholar 

  • Omar R, Pappolla M, Saran B (1990b) Heat shock protein response in alcoholic liver disease. Lab Med 21:811–814

    Google Scholar 

  • Pappolla M, Omar R, Saran B (1989) The “normal” brain: Abnormal ubiquitinilated deposits highlight an age-related phenomenon. Am J Pathol 135:585–591

    Google Scholar 

  • Pappolla M, Alzofon J, McMahon J, et al (1990a), Ultrastructural evidence that insoluble microtubules are components of the neurofibrillary tangle. Eur Arch Psychiatry Neurol Sci 239:314–319

    Google Scholar 

  • Pappolla M, Omar R, Saran B, et al (1990b) Heat shock proteins in dementia and degenerative nervous system disorders. Ment Illness Neurol Disord 4:12–13

    Google Scholar 

  • Pappolla M, Omar R, Kim K, et al (1992) Immunohistochemical evidence of oxidative stress in Alzheimer's disease. Am J Pathol 140:621–628

    Google Scholar 

  • Perez N, Sugar J, Charya S, et al (1991) Increases synthesis and accumulation of heat shock 70 proteins in Alzheimer's disease. Mol Brain Res 11:249–254

    Google Scholar 

  • Perry G, Friedman R, Shaw G, et al (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer's disease brains. Proc Natl Acad Sci USA 84:3033–3036

    Google Scholar 

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

    Google Scholar 

  • Privale C, Fridovich I (1987) Induction of superoxide dismutase inEscherichia coli by heat shock. Proc Natl Acad Sci USA 84:2723–2726

    Google Scholar 

  • Rechsteiner M (1988) Ubiquitin. Plenum Press, New York

    Google Scholar 

  • Ropp M, Courgeon A, Calvayrac R, Best-Belpomme M (1983) The possible role of the superoxide ion in the induction of heatshock and specific proteins in aerobicDrosophila cells during return to normoxia after a period of anaerobiosis. Can J Biochem Cell Biol 61:456–461

    Google Scholar 

  • Salo D, Donovan C, Davie KJ (1991) HSP 70 and other heat shock or oxidative stress proteins are induced in skeletal muscle, heart and liver during exercise. Free Radic Biol Med 11:239–246

    Google Scholar 

  • Schlesinger M (1986) Heat shock proteins. The search for function. J Cell Biol 103:321–326

    Google Scholar 

  • Schroeder F (1984) Role of membrane lipids asymmetry in aging. Neurobiol Aging 5:323:333

    Google Scholar 

  • Sciandra J, Subjeck J, Hughes C (1984) Induction of glucose-related proteins during anaerovic exposure and of heart shockproteins after reoxygenation. Proc Natl Acad Sci USA 81:4843–4847

    Google Scholar 

  • Somerville M, Percy M, Bergeron C, et al (1991) Localization and quantitation of 68 kDa neurofilament and superoxide dismutase-1 mRNA in Alzheimer brains. Mol Brain Res 9:1–8

    Google Scholar 

  • Subbarao K, Richardson S, Aug L (1990) Autopsy samples of Alzheimer's cortex show increased peroxidation in vitro. J Neurochem 55:342–345

    Google Scholar 

  • Sugimoto T, Tatsumi E, Kemshead J, et al (1984) Determination of cell surface membrane antigens common to both human neuroblastoma and leukemia-lymphoma cell lines by a panel of 38 monoclonal antibodies. J Natl Cancer Inst 73:51–57

    Google Scholar 

  • Volicer L, Crino P (1990) Involvement of free radicals in dementia of the Alzheimer type: a hypothesis. Neurobiol Aging 11:567–571

    Google Scholar 

  • Welch WJ, Mizzen LA, Arrigo AP (1989) Structure and function of mammalian stress proteins: In: Pardue ML, Feramisco JR, Lidquist S (eds) Stress induced proteins. Liss, New York p. 187

    Google Scholar 

  • Zelman F, Thienhaus O, Bosmann B (1989) Superoxide dismutase activity in Alzheimer's disease: possible mechanism for paired helical filament formation. Brain Res 476:160–162

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Omar, R., Pappolla, M. Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: Relevance to neurodegenerative disease. Eur Arch Psychiatry Clin Nuerosci 242, 262–267 (1993). https://doi.org/10.1007/BF02190384

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02190384

Key words

Navigation