Metals and Stress Proteins

  • P. L. Goering
  • B. R. Fisher
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 115)


Prokaryotic and eukaryotic cells respond to physical and chemical stressors or stress by increasing the transcription of specific genes that encode for a small class of proteins termed heat shock proteins (hsps). This response is believed to represent a transient reprogramming of gene expression and biological activity which serves to protect sensitive cellular components from irreversible damage and assists in the rapid recovery after the stress is removed or ceases. The changes in gene expression associated with this response following exposure to a stimulus are rapid, and result in both increased de novo synthesis and accumulation of stress proteins. Originally termed the heat shock response because of the induction of these proteins following hyperthermia (RItossa 1962), the signaling mechanism involved in its initiation is sensitive to a variety of physical and chemical insults, including metals (NOver 1991). Because the response can be initiated by a variety of stressors it is generically referred to as the “stress response.” In this review, for convention and to avoid confusion, we have adopted the use of the term “stress proteins” when referring to classic hsps and other stress proteins. Therefore, the hsps will be considered as a subset of the stress proteins, and reference to hsps will be used only when deemed necessary, e.g., when referring to specific references and studies describing specific hsps.


Heat Shock Heat Shock Protein Heme Oxygenase Stress Protein Heat Shock Response 
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.


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  1. Al-Aoukaty A, Appanna VD, Falter H (1992) Gallium toxicity and adaptation on Pseudomonas fluorescens. FEMS Microbiol Lett 71:265–272PubMedGoogle Scholar
  2. Amaral MD, Galego L, Rodrigues-Pousada C (1988) Stress response of Tetrahymena pyriformis to arsenite and heat shock:differences and similarities. Eur J Biochem 171:463–470PubMedGoogle Scholar
  3. Ananthan J, Goldberg AL, Voellmy R (1986) Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science 232:522–524PubMedGoogle Scholar
  4. Aoki Y, Lipsky MM, Fowler BA (1990) Alterations in protein synthesis in primary cultures of rat kidney proximal tubule epithelial cells by exposure to gallium, indium, and arsenite. Toxicol Appl Pharmacol 106:462–468PubMedGoogle Scholar
  5. Arrigo AP, Suhan JP, Welch WJ (1988) Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein. Mol Cell Biol 8:5059–5071PubMedGoogle Scholar
  6. Atkinson BG, Cunningham T, Dean RL, Somerville M (1983) Comparison of the effects of heat shock and metal-ion stress on gene expression in cells undergoing myogenesis. Can J Biochem Cell Biol 61:404–413PubMedGoogle Scholar
  7. Bauman JW, Liu J, Klaassen CD (1993) Production of metallothionein and heat-shock proteins in response to metals. Fundam Appl Toxicol 21:15–22PubMedGoogle Scholar
  8. Beckmann RP, Mizzen LA, Welch WJ (1990) Interaction of hsp70 with newly synthesized proteins:implications for protein folding and assembly. Science 248:850–854PubMedGoogle Scholar
  9. Blake MJ, Gershom D, Fargnoli J, Holbrook NJ (1990) Discordant expression of heat shock protein mRNAs in tissues of heat-stressed rats. J Biol Chem 265:15275–15279PubMedGoogle Scholar
  10. Blom A, Harder W, Matin A (1992) Unique and overlapping pollutant stress proteins of Escherichia coli. Appl Environ Microbiol 58:331–334PubMedGoogle Scholar
  11. Bournias-Vardiabasis N, Buzin C, Flores J (1990) Differential expression of heat shock proteins in Drosophila embryonic cells following metal ion exposure. Exp Cell Res 189:177–182PubMedGoogle Scholar
  12. Bruce JL, Price BD, Coleman CN, Calderwood SK (1993) Oxidative injury rapidly activates the heat shock transcription factor but fails to increase levels of heat shock proteins. Cancer Res 53:12–15PubMedGoogle Scholar
  13. Bunch TA, Grinblat Y, Goldstein LS (1988) Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells. Nucleic Acids Res 16:1043–1061PubMedGoogle Scholar
  14. Burgman PW, Kampinga HH, Konings AW (1993) Possible role of localized protein denaturation in the mechanism of induction of thermotolerance by heat, sodium-arsenite and ethanol. Int J Hyperthermia 9:151–162PubMedGoogle Scholar
  15. Cajone F, Bernelli-Zazzera A (1988) Oxidative stress induces a subset of heat shock proteins in rat hepatocytes and MH1C1 cells. Chem Biol Interact 65:235–246PubMedGoogle Scholar
  16. Caltabiano MM, Koestler TP, Poste G, Greig RG (1986a) Induction of 32- and 34- kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. J Biol Chem 261:13381–13386PubMedGoogle Scholar
  17. Caltabiano MM, Koestler TP, Poste G, Greig RG (1986b) Induction of mammalian stress proteins by a triethylphosphine gold compound used in the therapy of rheumatoid arthritis. Biochem Biophys Res Commum 138:1074–1080Google Scholar
  18. Caltabiano MM, Poste G, Greig RG (1988) Induction of the 32-kD human stress protein by auranofin and related triethylphosphine gold analogs. Biochem Pharmacol 37:4089–4093PubMedGoogle Scholar
  19. Carr BI, Huang TH, Buzin CH, Itakura K (1986) Induction of heat shock gene expression without heat by hepatocarcinogens and during hepatic regeneration in rat liver. Cancer Res 46:5106–5111PubMedGoogle Scholar
  20. Carson-Jurica MA, Lee AT, Dobson AW, Conneely OM, Schräder WT, O’Malley BW (1989) Interaction of the chicken progesterone receptor with heat shock protein (hsp) 90. J Steroid Biochem 34:1–9PubMedGoogle Scholar
  21. Cervera J (1985) Induction of self-tolerance and enhanced stress protein synthesis in L-132 cells by cadmium chloride and by hyperthermia. Cell Biol Int Rep 9:131–141PubMedGoogle Scholar
  22. Cheng M, Hartl F, Martin J, Pollock R, Kalousek F, Neupert W, Hallberg E, Hallberg R, Horwich A (1989) Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337:620–625PubMedGoogle Scholar
  23. Cherian MG, Howell SB, Imura N, Klaassen CD, Koropatnick J, Lazo JS, Waalkes MP (1994) Role of metallothionein in carcinogenesis. Toxicol Appl Pharmacol 126:1–5PubMedGoogle Scholar
  24. Chirico W, Waters MG, Blobel G (1988) 70K heat shock related proteins stimulate protein translocation into microsomes. Nature 332:805–810PubMedGoogle Scholar
  25. Christie NT, Costa M (1984) In vitro assessment of the toxicity of metal compounds. Biol Trace Elem Res 6:139–158Google Scholar
  26. Ciavarra RP, Simeone A (1990a) T lymphocyte stress response:I. Induction of heat shock protein synthesis at febrile temperatures is correlated with enhanced resistance to hyperthermic stress but not to heavy metal toxicity or dexamethasone-induced immunosuppression. Cell Immunol 129:363–376Google Scholar
  27. Ciavarra RP, Simeone A (1990b) T lymphocyte stress reponse. II. Protection of translation and DNA replication against some forms of stress by prior hyperthermic stress. Cell Immunol 131:11–26Google Scholar
  28. Clerget M, Polla BS (1990) Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages. Proc Natl Acad Sci USA 87:1081–1085PubMedGoogle Scholar
  29. Cochrane BJ, Irby RB, Snell TW (1991) Effects of copper and tributyltin on stress protein abundance in the rotifer Brachionus plicatilis. Comp Biochem Physiol 98C:385–390Google Scholar
  30. Cohen DS, Palmer E, Welch WJ, Sheppard D (1991) The response of guinea pig airway epithelial cells and alveolar macrophages to environmental stress. Am J Respir Cell Mol Biol 5:133–143PubMedGoogle Scholar
  31. Committee on Biological Markers (1987) Biological markers in environmental health research. Environ Health Perspect 74:3–9Google Scholar
  32. Coogan TP, Bare RM, Waalkes MP (1992) Cadmium-induced DNA damage:effects of zinc pretreatment. Toxicol Appl Pharmacol 113:227–233PubMedGoogle Scholar
  33. Coogan TP, Bare RM, Bjornson EJ, Waalkes MP (1994) Enhanced metallothionein gene expression protects against cadmium genotoxicity in cultured rat liver cells. J Toxicol Environ Health (in press)Google Scholar
  34. Courgeon A-M, Maisonhaute C, Best-Belpomme M (1984) Heat shock proteins are induced by cadmium in Drosophila cells. Exp Cell Res 153:515–521PubMedGoogle Scholar
  35. Darasch S, Mosser DD, Bols NC, Heikkila JJ (1988) Heat shock gene expression on Xenopus laevis A6 cells in response to heat shock and sodium arsenite treatments. Biochem Cell Biol 66:862–870PubMedGoogle Scholar
  36. Deaton MA, Bowman PD, Jones GP, Powanda MC (1990) Stress protein synthesis in human keratinocytes treated with sodium arsenite, phenyldichloroarsine, and nitrogen mustard. Fundam Appl Toxicol 14:471–476PubMedGoogle Scholar
  37. De Jong WW, Hoekman WA, Mulders JW, Bloemendal H (1986) Heat shock response in the rat lens. J Cell Biol 102:104–111PubMedGoogle Scholar
  38. Delpino A, Spinsanti P, Mattei E, Mileo AM, Vismara D, Ferrini U (1992) Identification of a 66 kD heat shock protein (HSP) induced in M-14 human melanoma cells by severe hyperthermic treatment. Melanoma Res 2:369–375PubMedGoogle Scholar
  39. Donati YR, Kantengwa S, Polla BS (1991) Phagocytosis and heat shock response in human monocytes-macrophages. Pathobiology 59:156–161PubMedGoogle Scholar
  40. Duncan RF, Hershey JWB (1987) Translational repression by chemical inducers of the stress response occurs by different pathways. Arch Biochem Biophys 256:651–661PubMedGoogle Scholar
  41. Eaton DL, Stacey NH, Wong K-L, Klaassen CD (1980) Dose-response effects of various metal ions on rat liver metallothionein, glutathione, heme oxygenase, and cytochrome P-450. Toxicol Appl Pharmacol 55:393–402PubMedGoogle Scholar
  42. Edwards MJ, Marks R, Dykes PJ, Merrett VR, Morgan HE, O’Donovan MR (1991) Heat shock proteins in cultured human keratinocytes and fibroblasts. J Invest Dermatol 96:392–396PubMedGoogle Scholar
  43. Ewing JF, Maines MD (1991) Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain:heme oxygenase 2 is not a heat shock protein. Proc Natl Acad Sci USA 88:5364–5368PubMedGoogle Scholar
  44. Ewing JF, Maines MD (1993) Glutathione depletion induces heme oxygenase-1 (HSP32) mRNA and protein in rat brain. J Neurochem 60:1512–1519PubMedGoogle Scholar
  45. Ewing JF, Haber SN, Maines MD (1992) Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain:hyperthermia causes rapid induction of mRNA and protein. J Neurochem 58:1140–1149PubMedGoogle Scholar
  46. Ferm VH, Layton WM Jr (1979) Reduction in cadmium teratogenesis by prior cadmium exposure. Environ Res 18:347–350PubMedGoogle Scholar
  47. Fischbach M, Sabbioni E, Bromley P (1993) Induction of the human growth hormone gene placed under human hsp70 promoter control in mouse cells:a quantitative indicator of metal toxicity. Cell Biol Toxicol 9:177–188PubMedGoogle Scholar
  48. Fowler BA, Silbergeld EK (1989) Occupational diseases — new workforces, new workplaces. Ann NY Acad Sci 572:46–54PubMedGoogle Scholar
  49. Fowler BA, Abel J, Elinder CG, Hapke HJ, Kagi JHR, Kleiminger J, Kojima Y, Schoot-Uiterkamp AJM, Silbergeld EK, Silver S, Summer KH, Williams RJP (1984) Structure, mechanism, and toxicity. In:Nriagu JU (ed) Changing metal cycles and human health. Springer, Berlin Heidelberg New York, pp 391–404Google Scholar
  50. Gerner EW, Schneider MJ (1975) Induced thermal resistance in HeLa cells. Nature 256:500–502PubMedGoogle Scholar
  51. Glaven JA, Gandley RE, Fowler BA (1991) Biological indicators of cadmium exposure, Chap 67. Methods Enzymol 205:592–599PubMedGoogle Scholar
  52. Goering PL, Klaassen CD (1983) Altered subcellular distribution of cadmium following cadmium pretreatment:possible mechanism of tolerance to cadmium-induced lethality. Toxicol Appl Pharmacol 70:195–203PubMedGoogle Scholar
  53. Goering PL, Klaassen CD (1984) Zinc-induced tolerance to cadmium hepatotoxicity. Toxicol Appl Pharmacol 74:299–307PubMedGoogle Scholar
  54. Goering PL, Fisher BR, Chaudhary PP, Dick CA (1992) Relationship between stress protein induction in rat kidney by mercuric chloride and nephrotoxicity. Toxicol Appl Pharmacol 113:184–191PubMedGoogle Scholar
  55. Goering PL, Fisher BR, Kish CL (1993a) Stress protein synthesis induced in rat liver by cadmium precedes hepatotoxicity. Toxicol Appl Pharmacol 122:139–148PubMedGoogle Scholar
  56. Goering PL, Fisher BR, Kimmel CA, Kimmel GL (1993b) Stress proteins as bio-markers of toxicity. In:Travis CC (ed) Use of biomarkers in assessing health and environmental impacts of chemical pollutants. Plenum, New York, pp 95–99Google Scholar
  57. Goering PL, Kish CL, Dick SE (1993c) Stress protein synthesis induced by cadmium in rat hepatocyte primary cultures. Toxicologist 13:160 (abstract)Google Scholar
  58. Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1–14PubMedGoogle Scholar
  59. Hamer DH (1986) Metallothionein. Annu Rev Biochem 55:913–951PubMedGoogle Scholar
  60. Hamet P (1992) Abnormal hsp70 gene expression:its potential key role in metabolic defects in hypertension. Clin Exp Pharmacol Physiol [Suppl] 20:53–59Google Scholar
  61. Hansen DK, Anson JF, Hinson WG, Pipkin JL Jr (1988) Phenytoin-induced stress protein synthesis in mouse embryonic tissue. Proc Soc Exp Biol Med 189:136–140PubMedGoogle Scholar
  62. Hashiba H, Hosoi J, Karasawa M, Yamada S, Nose K, Kuroki T (1989) Induction of metallothionein mRNA by tumor promoters in mouse skin and its constitutive expression in papillomas. Mol Carcinog 2:95–100PubMedGoogle Scholar
  63. Hatayama T, Tsukimi Y, Wakatsuki T, Kitamura T, Imahara H (1991) Different induction of 70 000-Da heat shock protein and metallothionein in HeLa cells by copper. J Biochem 110:726–731PubMedGoogle Scholar
  64. Hatayama T, Tsukimi Y, Wakatsuki T, Kitamura T, Imahara H (1992) Characteristic induction of 70 000-Da heat shock protein and metallothionein by zinc in HeLa cells. Mol Cell Biochem 112:143–153PubMedGoogle Scholar
  65. Heikkila JJ, Darasch SP, Mosser DD, Bols NC (1987) Heat and sodium arsenite act synergistically on the induction of heat shock gene expression in Xenopus laevis A6 cells. Biochem Cell Biol 65:310–316PubMedGoogle Scholar
  66. Hemmingsen SM, Woolford C, van de Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ (1988) Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 33:330–334Google Scholar
  67. Hendrick JP, Hartl F-U (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62:349–384PubMedGoogle Scholar
  68. Hightower LE (1991) Heat shock, stress proteins, chaperones, and proteotoxicity. Cell 66:191–197PubMedGoogle Scholar
  69. Hiwasa T, Sakiyama S (1986) Increase in the synthesis of a 32 000 Mr protein in BALB/C 3T3 cells after treatment with tumor promoters, chemical carcinogens, metal salts and heat shock. Cancer Res 46:2474–2481PubMedGoogle Scholar
  70. Hiwasa T, Fujimura S, Sakiyama S (1982) Tumor promoters increase the synthesis of a 32 000-dalton protein in BALB/c 3T3 cells. Proc Natl Acad Sci USA 79:1800–1804PubMedGoogle Scholar
  71. Honda K, Hatayama T, Takahashi K, Yukioka M (1992) Heat shock proteins in human and mouse embryonic cells after exposure to heat shock or teratogenic agents. Teratogenesis Carcinog Mutagen 11:235–244Google Scholar
  72. Howard KJ, Holley SJ, Yamamoto KR, Distelhorst CW (1990) Mapping the HSP90 binding region of the glucocorticoid receptor. J Biol Chem 265:11928–11935PubMedGoogle Scholar
  73. Imura N, Satoh M, Naganuma A (1991) Possible application of metallothionein in cancer therapy. In:Klaassen CD, Suzuki KT (eds) Metallothionein in biology and medicine. CRC Press, Boca Raton, pp 375–382Google Scholar
  74. Ito T, Sawauchi K (1966) Inhibitory effects on cadmium-induced testicular damage by pretreatment with smaller cadmium doses. Okajimas Folia Anat Jpn 42:107–117PubMedGoogle Scholar
  75. Johnston RN, Kucey BL (1988) Competitive inhibition of hsp70 gene expression causes thermosensitivity. Science 242:1551–1554PubMedGoogle Scholar
  76. Kägi JHR, Kojima Y (1987) Chemistry and biochemistry of metallothionein. Experientia [Suppl] 52:25–61Google Scholar
  77. Kampinga HH, Brunsting JF, Konings AW (1992) Acquisition of thermotolerance induced by heat and arsenite in HeLa S3 cells:multiple pathways to induce tolerance? J Cell Physiol 150:406–416PubMedGoogle Scholar
  78. Kantengwa S, Polla BS (1993) Phagocytosis of Staphylococcus aureus induces a selective stress response in human monocytes-macrophages (M phi):modulation by M phi differentiation and by iron. Infect Immunol 61:1281–1287Google Scholar
  79. Kapoor M, Sveenivasan GM (1988) The heat shock response of Neurospora crassa:stress-induced thermotolerance in relation to peroxidase and superoxide dismutase levels. Biochem Biophys Res Commun 156:1097–1102PubMedGoogle Scholar
  80. Kapron-Bras CM, Hales BF (1992) Genetic differences in heat-induced tolerance to cadmium in cultured mouse embryos are not correlated with changes in a 68-kD heat shock protein. Teratology 46:191–200PubMedGoogle Scholar
  81. Kasprzak KS (1991) The role of oxidative damage in metal carcinogenicity. Chem Res Toxicol 4:604–615PubMedGoogle Scholar
  82. Katayose D, Isoyama S, Fujita H, Shibahara S (1993) Separate regulation of heme oxygenase and heat shock protein 70 mRNA expression in the rat heart by hemodynamic stress. Biochem Biophys Res Commun 191:587–594PubMedGoogle Scholar
  83. Kaufmann SHE (1990) Heat shock proteins and the immune response. Immunol Today 11:129–136PubMedGoogle Scholar
  84. Keyse SM, Tyrrell RM (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 262:14821–14825PubMedGoogle Scholar
  85. Keyse M, Tyrrell 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 86:99–103PubMedGoogle Scholar
  86. Kohane DS, Sarzani R, Schwartz JH, Chobanian AV, Brecher P (1990) Stress- induced proteins in aortic smooth muscle cells and aorta of hypertensive rats. Am J Physiol 258:H1699–H1705PubMedGoogle Scholar
  87. Köhler HR, Triebskorn R, Stöcker W, Kloetzel PM, Alberti G (1992) The 70 kD heat shock protein in soil invertebrates:a possible tool for monitoring environmental toxicants. Arch Environ Contam Toxicol 22:334–338PubMedGoogle Scholar
  88. Kontosoglou TE, Banerjee D, Cherian MG (1989) Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch [A] 415:545–549Google Scholar
  89. Lai Y, Shen C, Cheng T, Hou M, Lee W (1993) Enhanced phosphorylation of a 65kDa protein is associated with rapid induction of stress proteins in 9L rat brain tumor cells. J Cell Biochem 51:369–379PubMedGoogle Scholar
  90. Landry J, Bernier D, Chretien P, Nicole LM, Tanguay RM, Marceau N (1982) Synthesis and degradation of heat shock proteins during development and decay of thermotolerance. Cancer Res 42:2457–2461PubMedGoogle Scholar
  91. Lavoie JN, Gingras-Breton G, Tanguay RM, Landry J (1993) Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J Biol Chem 268:3420–3429PubMedGoogle Scholar
  92. Leber AP, Miya TS (1976) A mechanism for cadmium and zinc-induced tolerance to cadmium toxicity:involvement of metallothionein. Toxicol Appl Pharmacol 37:403–414PubMedGoogle Scholar
  93. Lee KJ, Hahn GM (1988) Abnormal proteins as the trigger for the induction of stress responses:heat, diamide, and sodium arsenite. J Cell Physiol 136:411–420PubMedGoogle Scholar
  94. Lee YJ, Dewey WC (1987) Effect of cycloheximide or puromycin on induction of thermotolerance by sodium arsenite in Chinese hamster ovary cells:involvement of heat shock proteins. J Cell Physiol 132:41–48PubMedGoogle Scholar
  95. Lee YJ, Dewey WC (1988) Thermotolerance induced by heat, sodium arsenite, or puromycin:its inhibition and differences between 43 degrees C and 45 degrees C. J Cell Physiol 135:397–406PubMedGoogle Scholar
  96. Lee YJ, Curetty L, Corry PM (1991) Differences in preferential synthesis and redistribution of HSP70 and HSP28 families by heat shock or sodium arsenite in Chinese hamster ovary cells. J Cell Physiol 149:77–87PubMedGoogle Scholar
  97. Levinson W, Oppermann H, Jackson J (1980) Transition series metals and sulfhydryl reagents induce the synthesis of four proteins in eukaryotic cells. Biochim Biophys Acta 606:170–180PubMedGoogle Scholar
  98. Li GC (1983) Induction of thermotolerance and enhanced heat shock protein synthesis in Chinese hamster fibroblasts by sodium arsenite and by ethanol. J Cell Physiol 115:116–122PubMedGoogle Scholar
  99. Li GC, Laszlo A (1985) Animo acid analogs while inducing heat shock proteins sensitize CHO cells to thermal damage. J Cell Physiol 122:9197Google Scholar
  100. Li GC, Werb Z (1982) Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblast. Proc Natl Acad Sci USA 79:3218–3222PubMedGoogle Scholar
  101. Löw-Friedrich I, Schoeppe W (1991) Effects of calcium channel blockers on stress protein synthesis in cardiac myocytes. J Cardiovasc Pharmacol 17:800–806PubMedGoogle Scholar
  102. Maines MD (1988) Heme oxygenase:function, Multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557–2568PubMedGoogle Scholar
  103. Maines MD, Kappas A (1977) Metals as regulators of heme metabolism:physiological and toxicological implications. Science 198:1215–1221PubMedGoogle Scholar
  104. Maines MD, Chung A-S, Kutty RK (1982) Inhibition of testicular heme oxygenase activity by cadmium:a novel cellular response. J Biochem 257:14116–14121Google Scholar
  105. Maines MD, Mayer RD, Ewing JF, McCoubrey WK Jr (1993) Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion:possible role of heme as both promoter of tissue damage and regulator of HSP32. J Pharmacol Exp Ther 264:457–462PubMedGoogle Scholar
  106. Matsubara J, Tajima Y, Karasawa M (1987) Promotion of radioresistance by metallothionein induction prior to irradiation. Environ Res 43:66–74PubMedGoogle Scholar
  107. Miller L, Qureshi MA (1992) Heat-shock protein synthesis in chicken macrophages:influence of in vivo and in vitro heat shock, lead acetate, and lipopolysaccharide. Poult Sci 71:988–998PubMedGoogle Scholar
  108. Mirkes PE (1987) Hyperthermia-induced heat shock response and thermotolerance in postimplantation rat embryos. Dev Biol 119:115–122PubMedGoogle Scholar
  109. Mirkes PE, Cornel L (1992) A comparison of sodium arsenite- and hyperthermia- induced stress responses and abnormal development in cultured postimplantation rat embryos. Teratology 46:251–259PubMedGoogle Scholar
  110. Mirkes PE, Doggett B (1992) Accumulation of heat shock protein 72 in postimplantation rat embryos after exposure to various periods of hyperthermia in vitro:evidence that heat shock protein 72 is a biomarker of heat-induced embryo toxicity. Teratology 46:301 - 309PubMedGoogle Scholar
  111. Misra S, Zararullah M, Price-Haughey J, Gedamu L (1989) Analysis of stress- induced gene expression in fish cell lines exposed to heavy metals and heat shock. Biochim Biophys Acta 1007:325–333PubMedGoogle Scholar
  112. Mitani K, Fujita H, Sassa S, Kappas A (1990) Activation of heme oxygenase and heat shock protein 70 genes by stress in human hepatoma cells. Biochem Biophys Res Commun 166:1429–1434PubMedGoogle Scholar
  113. Moretti-Rojas I, Fugua SA, Montgomery RA, McGuire WL (1988) A cDNA for estradiol-regulated 24k protein:control of mRNA levels in MCF-7 cells. Breast Cancer Treat 11:155 - 163Google Scholar
  114. Morimoto RI, Tissieres A, Georgopoulos C (1990) The stress response, function of the proteins, and perspectives. In:Morimoto RI, Tissières A, Georgopoulos C (eds) Stress proteins in biology and medicine. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, pp 1–36Google Scholar
  115. Morimoto RI, Sarge KD, Abravaya K (1992) Transcriptional regulation of heat shock genes. J Biol Chem 267:21987–21990PubMedGoogle Scholar
  116. Morton KA, Alazaraki NP, Datz FL, Taylor AT (1988) Uptake of cadmium-109, a metallothionein-binding radiometal, by tumors in mice as a function of the transformed phenotype. Invest Radiol 23:200–204PubMedGoogle Scholar
  117. Murakami T, Ohmori H, Katoh T, Abe T, Higashi K (1991) Cadmium causes increases of N-myc and multidrug-resistance gene mRNA in neuroblastoma cells. Sangyo Ika Daigaku Zasshi 13:271–278PubMedGoogle Scholar
  118. Nartley N, Cherian MG, Banerjee D (1987) Immunohistochemical localization of metallothionein in human thyroid tumors. Am J Pathol 129:177–182Google Scholar
  119. Nover L (1991) Heat shock response. CRC Press, Boca RatonGoogle Scholar
  120. Ödberg-Ferragut C, Espigares M, Dive D (1991) Stress protein synthesis, a potential toxicity marker in Escherichia coli. Ecotoxicol Environ Safety 21:275–282PubMedGoogle Scholar
  121. Palmiter R (1987) Molecular biology of metallothionein gene expression. Experientia [Suppl] 52:63–80Google Scholar
  122. Pannekoek Y, van Putten JP, Dandert J (1992) Identification and molecular analysis of a 63-kilodalton stress protein from Neisseria gonorrhoeae. J Bacteriol 174:6928–6937PubMedGoogle Scholar
  123. Pelham HRB (1982) A regulatory upstream promoter element in the Drosophila hsp70 heat shock gene. Cell 30:517–528PubMedGoogle Scholar
  124. Pelham HRB (1986) Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell 46:959–961PubMedGoogle Scholar
  125. Riabowol KT, Mizzen LA, Welch WJ (1988) Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science 242:433–436PubMedGoogle Scholar
  126. Ritossa FM (1962) A new puffing pattern induced by heat shock and DNP in Drosophila. Experientia 18:571–573Google Scholar
  127. Roberts SA, Miya TS, Schnell RC (1976) Tolerance development to cadmium-induced alteration of drug action. Res Commun Chem Pathol Pharmacol 14:197–200PubMedGoogle Scholar
  128. Roccheri MC, La Rosa M, Ferraro MG, Cantone M, Cascino D, Giudice G, Sconzo G (1988) Stress proteins by zinc ions in sea urchin embryos. Cell Differ 24:209–213PubMedGoogle Scholar
  129. Rodenhiser D, Jung JH, Atkinson BG (1985) Mammalian lymphocytes:stress-induced synthesis of heat-shock proteins in vitro and in vivo. Can J Biochem Cell Biol 63:711–722PubMedGoogle Scholar
  130. Rodenhiser DI, Jung JH, Atkinson BG (1986) The synergistic effect of hyperthermia and ethanol on changing gene expression of mouse lymphocytes. Can J Genet Cytol 28:1115–1124PubMedGoogle Scholar
  131. Rollet E, Lavoie JN, Landry L, Tanguay RM (1992) Expression of Drosophila’s 27kDa heat shock protein into rodent cells confers thermal resistance. Biochem Biophys Res Commun 185:116–120PubMedGoogle Scholar
  132. Rothman JE (1989) Polypeptide chain binding proteins:catalysts of proteins folding and related processes in cells. Cell 59:591–601PubMedGoogle Scholar
  133. Sanchez Y, Taulien J, Borkovich KA, Lindquist S (1992) Hsp104 is required for tolerance to many forms of stress. EMBO J 11:2357–2364PubMedGoogle Scholar
  134. Sanders BM (1990) Stress proteins:potential as multitiered biomarkers. In:McCarthy J, Shugart L (eds) Biological markers of environmental contamination. Lewis, Boca Raton, pp 165–191Google Scholar
  135. Sanders BM (1993) Stress proteins in aquatic organisms:an environmental perspective. Crit Rev Toxicol 23:49–75PubMedGoogle Scholar
  136. Sanders BM, Martin LS, Nelson WG, Phelps DK, Welch W (1991) Relationships between accumulation of a 60 kDa stress protein and scope-for-growth in Mytilus edulis exposed to a range of copper concentrations. Marine Environ Res 31:81–97Google Scholar
  137. Sato M, Ishizawa S, Yoshida T, Shibahara S (1990) Interaction of upstream stimulatory factor with the human heme oxygenase gene promoter. Eur J Biochem 188:231–237PubMedGoogle Scholar
  138. Sauk JJ, Norris K, Foster R, Moehring J, Somerman MJ (1988) Expression of heat stress proteins by human periodontal ligament cells. J Oral Pathol 17:496–499PubMedGoogle Scholar
  139. Saunders EL, Maines MD, Meredith MJ, Freeman ML (1991) Enhancement of heme oxygenase-1 synthesis by glutathione depletion in Chinese hamster ovary cells. Arch Biochem Biophys 288:368–373PubMedGoogle Scholar
  140. Schlesinger MJ (1990) Heat shock proteins. J Biol Chem 265:12111–12114PubMedGoogle Scholar
  141. Schmidt JA, Abdulla E (1988) Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response. J Immunol 141:2027–2034PubMedGoogle Scholar
  142. Sheffield WP, Shore GC, Randall SK (1990) Mitochondrial precursor protein:effects of 70-kilodalton heat shock protein on polypeptide folding, aggregation, and import competence. J Biol Chem 265:11069–11076PubMedGoogle Scholar
  143. Shelton KR, Todd JM, Egle PM (1986) The induction of stress-related proteins by lead. J Biol Chem 261:1935–1940PubMedGoogle Scholar
  144. Shibahara S, Müller RM, Taguchi H (1987) Transcriptional control of rat heme oxygenase by heat shock. J Biol Chem 262:12889–12892PubMedGoogle Scholar
  145. Shuman J, Przybyla A (1988) Expression of the 31-kDa stress protein in rat myoblasts and hepatocytes. DNA 7:475–482PubMedGoogle Scholar
  146. Silar P, Butler G, Thiele DJ (1991) Heat shock transcription factor activates transcription of the yeast metallothionein gene. Mol Cell Biol 11:1232–1238PubMedGoogle Scholar
  147. Squibb KS, Pritchard JB, Fowler BA (1984) Cadmium metallothionein nephropathy:ultrastructural/biochemical alterations and intracellular cadmium binding. J Pharmacol Exp Ther 229:311–321PubMedGoogle Scholar
  148. Stacey NH, Klaassen CD (1981) Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health 7:139–147PubMedGoogle Scholar
  149. Stegeman JJ, Brouwer M, Di Giulio RT, Forlin L, Fowler BA, Sanders BM, Van Veld PA (1992) Molecular responses to environmental contamination:enzyme and protein systems as indicators of chemical exposure and effect. In:Huggett RJ, Kimerle RA, Mehrle PM, Bergman HL (eds) Biomarkers:biochemical, physiological, and histological markers of anthropogenic stress. Lewis, Boca Raton, pp 235–335Google Scholar
  150. Stocker R, Glazer AN, Ames BN (1987a) Antioxidant activity of albumin-bound bilirubin. Proc Natl Acad Sci USA 84:5918–5922PubMedGoogle Scholar
  151. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987b) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1047PubMedGoogle Scholar
  152. Subjeck JR, Shyy T, Shen J, Johnson RJ (1983) Association between mammalian 110 000 dalton heat shock protein and nucleoli. J Cell Biol 97:1389–1398PubMedGoogle Scholar
  153. Tacchini L, Schiaffonati L, Pappalardo C, Gatti S, Bernelli-Zazzera A (1993) Expression of HSP 70, immediate-early response and heme oxygenase genes in ischemic-reperfused rat liver. Lab Invest 68:465–471PubMedGoogle Scholar
  154. Taketani S, Kohno H, Yoshinaga T, Tokunaga R (1988) Induction of heme oxygenase in rat hepatoma cells by exposure to heavy metals and hyperthermia. Biochem Int 17:665–672PubMedGoogle Scholar
  155. Taketani S, Kohno H, Yoshinaga T, Tokunaga R (1989) The human 32-kDa stress protein induced by exposure to arsenite and cadmium ions is heme oxygenase. FEBS Lett 245:173–176PubMedGoogle Scholar
  156. Taketani S, Sato H, Yoshinage T, Tokunaga R, Ishii T, Bannai S (1990) Induction in mouse peritoneal macrophages of 34 kDa stress protein and heme oxygenase by sulfhydryl-reactive agents. J Biochem 108:28–32PubMedGoogle Scholar
  157. Tamai KT, Gralla EB, Ellerby LM, Valentine JS, Thiele DJ (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc super-oxide dismutase. Proc Natl Acad Sci USA 90:8013–8017PubMedGoogle Scholar
  158. Thornalley PJ, Vasak M (1985) Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta 827:36–44PubMedGoogle Scholar
  159. Uney JB, Anderson BH Thomas SM (1993) Changes in heat shock protein 70 and ubiquitin mRNA levels in C1300 N2A mouse neuroblastoma cells following treatment with iron. J Neurochem 60:659–665PubMedGoogle Scholar
  160. Valone SE, Chikami GK, Miller VL (1993) Stress induction of the virulence proteins (SpvA, -B, and -C) from native plasmid pSDL2 of Salmonella dublin. Infect Immun 61:705–713PubMedGoogle Scholar
  161. Van Eden W (1991) Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. Immunol Rev 121:5–28PubMedGoogle Scholar
  162. Waalkes MP, Goering PL (1990) Metallothionein and other cadmium-binding proteins:recent developments. Chem Res Toxicol 3:281–288PubMedGoogle Scholar
  163. Waalkes MP, Ward JM (1989) Induction of hepatic metallothionein in male B6C3F1 mice exposed to hepatic tumor promoters:effects of phenobarbital, acetaminophen, sodium barbital, and di(2-ethylhexyl) phthalate. Toxicol Appl Pharmacol 100:217–226PubMedGoogle Scholar
  164. Watowich SS, Morimoto RI (1988) Complex regulation of heat shock- and glucose-responsive genes in human cells. Mol Cell Biol 8:393–405PubMedGoogle Scholar
  165. Welch WJ (1985) Phorbol ester, calcium ionophore, or serum added to quiescent rat embryo fibroblast cells all result in the elevated phosphorylation of two 28 000 dalton mammalian stress proteins. J Biol Chem 260:3058–3065PubMedGoogle Scholar
  166. Welch WJ (1987) The mammalian heat shock (or stress) response:a cellular defense mechanism. Adv Exp Med Biol 225:287–304PubMedGoogle Scholar
  167. Welch WJ (1990) The mammalian stress response:cell physiology and biochemistry of stress proteins. In:Morimoto RI, Tissieres A, Georgopoulos C (eds) Stress proteins in biology and medicine. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, pp 223–278Google Scholar
  168. Welch WJ (1992) Mammalian stress response:cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 72:1063–1081PubMedGoogle Scholar
  169. Welch WJ (1993) How cells respond to stress. Sci Am 268 (5):56–64PubMedGoogle Scholar
  170. Welch WJ, Mizzen LA (1988) Characterization of the thermotolerant cell. II. Effects on the intercellular distribution of heat-shock protein 70, intermediate filaments, and small nuclear ribonucleoprotein complexes. J Cell Biol 106:1117–1130PubMedGoogle Scholar
  171. Wiegant FA, van Bergen en Henegouwen PM, van Dongen G, Linnemans WA (1987) Stress-induced thermotolerance of the cytoskeleton of mouse neuroblastoma N2A cells and rat Reuber H35 hepatoma cells. Cancer Res 47:1674–1680PubMedGoogle Scholar
  172. Wilhelmsson A, Cuthill S, Denis M, Wikstrom AC, Gustafsson J A, Poellinger L (1990) The specific DNA binding activity of the dioxin receptor is modulated by the 90 kD heat shock protein. EMBO J 9:69–76PubMedGoogle Scholar
  173. Winfield JB, Jarjour WN (1991) Stress proteins, autoimmunity, and autoimmune disease. In:Kaufmann SH (ed) Heat shock proteins and immune response. Springer, Berlin Heidelberg New York, pp 161–189 (Current topics in microbiology and immunology, vol 167 )Google Scholar
  174. Woods JS, Carver GT, Fowler BA (1979) Altered regulation of hepatic heme metabolism by indium chloride. Toxicol Appl Pharmacol 49:455–461PubMedGoogle Scholar
  175. Woods JS, Fowler BA, Eaton DL (1984) Studies on the mechanisms of thallium mediated inhibition of hepatic mixed-function oxidase activity:correlation with inhibition of NADPH-cytochrome c (P-450) reductase. Biochem Pharmacol 33:571–576PubMedGoogle Scholar
  176. Wu BJ, Kingston RE, Morimoto RI (1986) Human HSP70 promoter contains at least two distinct regulatory domains. Proc Natl Acad Sci USA 83:629–633PubMedGoogle Scholar
  177. Wu C (1984a) Two protein-binding sites in chromatin implicated in the activation of heat shock genes. Nature 309:229–234PubMedGoogle Scholar
  178. Wu C (1984b) Activating protein factor binds in vitro to upstream control sequences in heat shock gene chromatin. Nature 311:81–84PubMedGoogle Scholar
  179. Yamada H, Koizumi S (1993) Induction of a 70-kDa protein in human lymphocytes exposed to inorganic heavy metals and toxic organic compounds. Toxicology 79:131–138PubMedGoogle Scholar
  180. Yoshida T, Biro P, Cohen T, Müller RM, Shibahara S (1988) Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem 171:457–461PubMedGoogle Scholar
  181. Yoshikawa H (1973) Preventive effects of pretreatment with cadmium on acute cadmium poisoning in rats. Ind Health 11:113–119Google Scholar
  182. Zeuthen ML, Howard DH (1989) Thermotolerance and the heat-shock response in Candida albicans. J Gen Microbiol 135:2509–2518PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • P. L. Goering
  • B. R. Fisher

There are no affiliations available

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