The cell in shock

  • M. M. Morales
  • H. Petrs-Silva
Conference paper


‘Cellular homeostasis’ is any of the processes involved in the maintenance of an internal equilibrium within a cell or between a cell and its external environment. The physical and biochemical parameters of physiological equilibrium conducive to eukaryotic cell function include availability and maintenance of nutrients, oxygenation, temperature, pH, and osmolality, but exposure to conditions when these parameters are outside the physiological ranges is considered to cause stress to the cell, leading to macromolecular damage. Many types of environmental stress have been shown to cause deleterious changes in cells, including osmotic stress [1], thermal stress [2], heavy metal stress [3], ionising radiation [4], baric stress [5], oxidative stress [6], chemical genotoxin stress [7], mechanical injury stress [8] and hypoxia/ischaemia [9].


Endoplasmic Reticulum Stress Unfold Protein Response Apoptosis Induce Factor Autophagic Cell Death Cell Death Differ 
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. 1.
    Ho SN (2006) Intracellular water homeostasis and the mammalian cellular osmotic stress response. J Cell Physiol 206(1):9–15PubMedCrossRefGoogle Scholar
  2. 2.
    Dewhirst MW, Vujaskovic Z, Jones, Thrall D (2005) Re-setting the biologic rationale for thermal therapy. Int J Hyperthermia 21(8):779–790PubMedCrossRefGoogle Scholar
  3. 3.
    Ong WY, Farooqui AA (2005) Iron, neuroinflammation, and Alzheimer’s disease. J Alzheimers Dis 8(2):183–200PubMedGoogle Scholar
  4. 4.
    Lobrich M, Kiefer J (2006) Assessing the likelihood of severe side effects in radiotherapy. Int J Cancer 118(11):2652–2656PubMedCrossRefGoogle Scholar
  5. 5.
    Somero GN (1992) Adaptations to high hydrostatic pressure. Annu Rev Physiol 54:557–577PubMedCrossRefGoogle Scholar
  6. 6.
    Butler D, Bahr BA (2006) Oxidative stress and lysosomes: CNS-related consequences and implications for lysosomal enhancement strategies and induction of autophagy. Antioxid Redox Signal 8(1–2):185–196PubMedCrossRefGoogle Scholar
  7. 7.
    Zhou C, Li Z, Diao H, Yu Y et al (2006) DNA damage evaluated by gamma H2AX foci formation by a selective group of chemical/physical stressors. Mutat Res 604(1–2):8–18PubMedGoogle Scholar
  8. 8.
    Garcia CS, Prota LF, Morales MM et al (2006) Understanding the mechanisms of lung mechanical stress. Braz J Med Biol Res 39(6):697–706PubMedCrossRefGoogle Scholar
  9. 9.
    Bazan NG, Palacios-Pelaez R, Lukiw WJ (2002) Hypoxia signaling to genes: significance in Alzheimer’s disease. Mol Neurobiol 26(2–3):283–298PubMedCrossRefGoogle Scholar
  10. 10.
    Kultz D (2003) Evolution of the stress proteome: from monophyletic origin to ubiquitous function. J Exp Biol 206:3119–3124PubMedCrossRefGoogle Scholar
  11. 11.
    Bakkenist CJ, Kastan MB (2004) Initiating cellular stress responses. Cell 2004 118:9–17PubMedCrossRefGoogle Scholar
  12. 12.
    Zhu WZ, Xie Y, Chen L et al (2006) Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury. J Mol Cell Cardiol 40(1):96–106PubMedCrossRefGoogle Scholar
  13. 13.
    Kultz D (2005) Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol 67:225–257PubMedCrossRefGoogle Scholar
  14. 14.
    Beere HM (2001) Stressed to death: regulation of apoptotic signaling pathways by the heat shock proteins. Sci STKE (93):RE1Google Scholar
  15. 15.
    Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13(3):363–373PubMedCrossRefGoogle Scholar
  16. 16.
    Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192(1):1–15PubMedCrossRefGoogle Scholar
  17. 17.
    Herr I, Debatin KM (2001) Cellular stress response and apoptosis in cancer therapy. Blood 98(9):2603–2614PubMedCrossRefGoogle Scholar
  18. 18.
    Ashburner M, Bonner JJ (1979) The induction of gene activity in Drosophila by heat shock. Cell 17(2):241–254PubMedCrossRefGoogle Scholar
  19. 19.
    Eichler TE, Ransom RF, Smoyer WE (2005) Differential induction of podocyte heat shock proteins by prolonged single and combination toxic metal exposure. Toxicol Sci 84(1):120–128PubMedCrossRefGoogle Scholar
  20. 20.
    Miles MF, Diaz JE, DeGuzman VS (1991) Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene transcription in NG108-15 neuroblastoma × glioma cells. J Biol Chem 266(4):2409–2414PubMedGoogle Scholar
  21. 21.
    Taggart MJ, Wray S (1998) Hypoxia and smooth muscle function: key regulatory events during metabolic stress. J Physiol 509(2):315–325PubMedCrossRefGoogle Scholar
  22. 22.
    Adams C, Rinne RW (1982) Stress protein formation: gene expression and environmental interaction with evolutionary significance. Int Rev Cytol 79:305–315PubMedCrossRefGoogle Scholar
  23. 23.
    Craig EA (1985) The heat shock response. CRC Crit Rev Biochem 18(3):239–280PubMedCrossRefGoogle Scholar
  24. 24.
    Becker J, Craig EA (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219:11–23PubMedCrossRefGoogle Scholar
  25. 25.
    Bond U (2006) Stressed out! Effects of environmental stress on mRNA metabolism. FEMS Yeast Res 6:160–170PubMedCrossRefGoogle Scholar
  26. 26.
    Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Invest 115(10):2633–2639PubMedCrossRefGoogle Scholar
  27. 27.
    Garrido C, Schmitt E, Cande C et al (2003) HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2(6):579–584PubMedGoogle Scholar
  28. 28.
    Creagh EM, Sheehan D, Cotter TG (2000) Heat shock proteins—modulators of apoptosis in tumor cells. Leukemia 14:1161–1173PubMedCrossRefGoogle Scholar
  29. 29.
    Cadenas E, Davies KJ (2000) Mitochondrial free radicals generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrari R, Guardigli G, Mele D et al (2004) Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des 10(14):1699–1711PubMedCrossRefGoogle Scholar
  31. 31.
    Chinopoulos C, Adam-Vizi V (2006) Calcium, mitochondria and oxidative stress in neuronal pathology. Novel aspects of an enduring theme. FEBS J 273(3):433–450PubMedCrossRefGoogle Scholar
  32. 32.
    Barja G (2002) Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med 33:1167–1172PubMedCrossRefGoogle Scholar
  33. 33.
    McEligot AJ, Yang S, Meyskens FL, Jr (2005) Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells. Annu Rev Nutr 25:261–295PubMedCrossRefGoogle Scholar
  34. 34.
    Dringen R (2005) Oxidative and antioxidative potential of brain microglial cells. Antioxid Redox Signal 7(9–10):1223–1233PubMedCrossRefGoogle Scholar
  35. 35.
    Hall JE, Guyton AC, Brands MW (1996) Pressure-volume regulation in hypertension. Kidney Int Suppl 55:S35–41PubMedGoogle Scholar
  36. 36.
    McManus ML, Churchwell KB, Strange K (1995) Regulation of cell volume in health and disease. N Engl J Med 333(19):1260–1266PubMedCrossRefGoogle Scholar
  37. 37.
    Lang F, Busch GL, Ritter M et al (1998) Functional significance of cell volume regulatory mechanisms. Physiol Rev 78(1):247–306PubMedGoogle Scholar
  38. 38.
    Morales MM, Nascimento DS, Capella MA et al (2001) Arginine vasopressin regulates CFTR and ClC-2 mRNA expression in rat kidney cortex and medulla. Pflugers Arch 443(2):202–211PubMedCrossRefGoogle Scholar
  39. 39.
    Dmitrieva NI, Cai Q, Burg MB (2004) Cells adapted to high NaCl havemany DNA breaks and impaired DNA repair both in cell culture and in vivo. Proc Natl Acad Sci USA 101:2317–2322PubMedCrossRefGoogle Scholar
  40. 40.
    Maloiy GMO, Magfarlane WV, Shkolnik A (1979) Mammalian herbivores. In: Maloiy GMO (ed) Comparative physiology of osmoregulation in animals. Academic Press, ?, pp 185–211Google Scholar
  41. 41.
    Dmitrieva NI, Burg MB (2004) Living with DNA breaks is an everyday reality for cells adapted to high NaCl. Cell Cycle 3:561–563PubMedGoogle Scholar
  42. 42.
    Zhang K, Kaufman RJ (2006) Protein folding in the endoplasmic reticulum and the unfolded protein response. Handb Exp Pharmacol 172:69–91PubMedGoogle Scholar
  43. 43.
    Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372–380PubMedCrossRefGoogle Scholar
  44. 44.
    Aridor M, Balch WE (1999) Integration of endoplasmic reticulum signaling in health and disease. Nat Med 5:745–751PubMedCrossRefGoogle Scholar
  45. 45.
    Lindholm D, Wootz H, Korhonen L (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13(3):385–392PubMedCrossRefGoogle Scholar
  46. 46.
    Urano F, Wang X, Bertolotti A et al (2000) Coupling of stress in the ER activation of JNK protein kinases by transmembrane protein kinase IRES1. Science 287:664–666PubMedCrossRefGoogle Scholar
  47. 47.
    Morishima N, Nakanishi K, Takenouchi H et al (2002) An ER stress-specific caspase cascade in apoptosis: cytochrome c independent activation of caspase-9 by caspase-12. J Biol Chem 3:3Google Scholar
  48. 48.
    Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13(3):363–373PubMedCrossRefGoogle Scholar
  49. 49.
    Kato T, Matsumura Y, Tsukanaka A et al (2004) Effect of low oxygen inhalation on changes in blood pH, lactate, and ammonia due to exercise. Eur J Appl Physiol 91(2–3):296–302PubMedCrossRefGoogle Scholar
  50. 50.
    Semenza GL (1999) Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15:551–578PubMedCrossRefGoogle Scholar
  51. 51.
    Ikeda E (2005) Cellular response to tissue hypoxia and its involvement in disease progression. Pathol Int 55(10):603–610PubMedCrossRefGoogle Scholar
  52. 52.
    Gruber M, Simon MC (2006) Hypoxia-inducible factors, hypoxia, and tumor angiogenesis. Curr Opin Hematol 13(3):169–174PubMedCrossRefGoogle Scholar
  53. 53.
    Fink T, Ebbesen P, Zachar V (2001) Quantitative gene expression profiles of human liver-derived cell lines exposed to moderate hypoxia. Cell Physiol Biochem 11:105–114PubMedCrossRefGoogle Scholar
  54. 54.
    Pugh CW, O-Rourke JF, Nagao M et al (1997) Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem 272(17):11205–11214PubMedCrossRefGoogle Scholar
  55. 55.
    Piper HM (1989) Energy deficiency, calcium overload or oxidative stress: possible causes of irreversible ischemic myocardial injury. Klin Wochenschr 67(9):465–476PubMedCrossRefGoogle Scholar
  56. 56.
    Wouters BG, Weppler SA, Koritzinsky M et al (2002) Hypoxia as a target for combined modality treatments. Eur J Cancer 38:240–257PubMedCrossRefGoogle Scholar
  57. 57.
    Feldman DE, Chauhan V, Koong AC (2005) The unfolded protein response: a novel component of the hypoxic stress response in tumors. Mol Cancer Res 3(11):597–605PubMedCrossRefGoogle Scholar
  58. 58.
    He B (2006) Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ 13(3):393–403PubMedCrossRefGoogle Scholar
  59. 59.
    Schroder M, Kaufman RJ (2006) Divergent roles of IRE1alpha and PERK in the unfolded protein response. Curr Mol Med 6(1):5–36PubMedCrossRefGoogle Scholar
  60. 60.
    Oteiza PI, Mackenzie GG (2005) Zinc, oxidant-triggered cell signaling, and human health. Mol Aspects Med 26(4—5):245–255PubMedCrossRefGoogle Scholar
  61. 61.
    Vaux DL, Weissman IL, Kim SK (1992) Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science 258(5090):1955–1957PubMedCrossRefGoogle Scholar
  62. 62.
    Oppenheim RW (1999) Programmed cell death. In: Zigmond MJ, Bloom FE, Landis SC et al (eds) Fundamental neuroscience. Academic Press, New York, pp 581–609Google Scholar
  63. 63.
    Williams GT, Smith CA, Spooncer E et al (1990) Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 343(6253):76–79PubMedCrossRefGoogle Scholar
  64. 64.
    Glucksmann A (1951) Cell deaths in normal vertebrate ontogeny. Biol Rev 26:59–86CrossRefGoogle Scholar
  65. 65.
    Sen S (1992) Programmed cell death: concept, mechanism and control. Biol Rev 67:287–319PubMedGoogle Scholar
  66. 66.
    Krantic S, Mechawar N, Reix S, Quirion R (2005) Molecular basis of programmed cell death involved in neurodegeneration. Trends Neurosci 28(12):670–676PubMedGoogle Scholar
  67. 67.
    Schimmer AD, Dalili S, Batey RA, Riedl SJ (2006) Targeting XIAP for the treatment of malignancy. Cell Death Differ 13(2):179–188PubMedCrossRefGoogle Scholar
  68. 68.
    Leist M, Jaattela M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2(8):589–598PubMedCrossRefGoogle Scholar
  69. 69.
    Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedGoogle Scholar
  70. 70.
    Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776PubMedCrossRefGoogle Scholar
  71. 71.
    Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5:897–907PubMedCrossRefGoogle Scholar
  72. 72.
    Ashkenazi A, Dixit VM (1998) Death receptors: Signaling and modulation. Science 281:1305–1308PubMedCrossRefGoogle Scholar
  73. 73.
    Shi Y (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9:459–470PubMedCrossRefGoogle Scholar
  74. 74.
    Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22(53):8543–8567PubMedCrossRefGoogle Scholar
  75. 75.
    Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12:1528–1534PubMedCrossRefGoogle Scholar
  76. 76.
    Kiffin R, Bandyopadhyay U, Cuervo AM (2006) Oxidative stress and autophagy. Antioxid Redox Signal 8(1–2):152–162PubMedCrossRefGoogle Scholar
  77. 77.
    Lee CY, Baehrecke EH (2001) Steroid regulation of autophagic programmed cell death during development. Development 128:1443–1455PubMedGoogle Scholar
  78. 78.
    Shimizu S, Kanaseki T, Mizushima N et al (2004) A role of Bcl-2 family of proteins in nonapoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221–1228PubMedCrossRefGoogle Scholar
  79. 79.
    Cande C, Cecconi F, Dessen P, Kroemer G (2002) Apoptosis inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? J Cell Sci 115:4727–4734PubMedCrossRefGoogle Scholar
  80. 80.
    Cande C, Vahsen N, Kouranti I et al (2004) AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 23(8):1514–1521PubMedCrossRefGoogle Scholar
  81. 81.
    Sperandio S, de Belle I, Bredesen DE (2000) An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci USA 97:14376–14381PubMedCrossRefGoogle Scholar
  82. 82.
    Brown JM, Wouters BG (2001) Apoptosis: mediator or mode of cell killing by anticancer agents? Drug Resist Updat 4:135–136PubMedCrossRefGoogle Scholar
  83. 83.
    Zong WX, Thompson CB (2006) Necrotic death as a cell fate. Genes Dev 20(1):1–15PubMedCrossRefGoogle Scholar
  84. 84.
    Waring P, Lambert D, Sjaarda A et al (1999) Increased cell surface exposure of phosphatidylserine on propidium iodide negative thymocytes undergoing death by necrosis. Cell Death Differ 6:624–637PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • M. M. Morales
    • 1
  • H. Petrs-Silva
    • 1
  1. 1.Instituto de Biofísica Carlos Chagas FilhoFederal University of Rio de JaneiroBrazil

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