Multiple Roles of the Calcium Ion in Cell Killing

  • Sten Orrenius
  • Pierluigi Nicotera
Part of the Advances in Research on Neurodegeneration book series (ARN, volume 2)

Abstract

The realization that the calcium ion is involved in the regulation of a large number of physiological processes has included the understanding that Ca2+ can play a determinant role in a variety of pathological and toxicological conditions. It has long been recognized that Ca2+ accumulates in necrotic tissue, and subsequent work has revealed that a disruption of intracellular Ca2+ homeostasis is frequently associated with the early development of cell injury (Fleckenstein et al., 1983; Jewell et al., 1982; Schanne et al., 1979). This led to the formulation of the calcium hypothesis of cell injury, which proposes that perturbation of the intracellular Ca2+ homeostasis may be a common step in the development of cytotoxicity.

Keywords

Mercury Adenosine Glucocorticoid Cyanide Thiol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arenas MJ, Morros RG, Wyllie AH (1990): Apoptosis — the role of the endonuclease. Am J Pathol 136:591–608Google Scholar
  2. Aw TY, Nicotera P, Manzo L, Orrenius S (1990): Tributyltin stimulates apoptosis in rat thymocytes. Arch Biochem Biophys 283:46–50PubMedCrossRefGoogle Scholar
  3. Barritt GJ, Parker JC, Wadsworth JC (1981): A kinetic analysis of the effect of adrenalin on calcium distribution in isolated rat liver parenchymal cells. J Physiol 312:29–55PubMedGoogle Scholar
  4. Bellomo G, Mirabelli F, Richelmi P, Malorni W, Iosi F, Orrenius S (1990): The cytoskeleton as a target in quinone toxicity. Free Radical Res Commun 8:391–399CrossRefGoogle Scholar
  5. Bellomo G, Perotti M, Taddei F, Mirabelli F, Finardi G, Nicotera P, Orrenius S (1992): Tumor necrosis factor α induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation. Cancer Res 52:1342–1346PubMedGoogle Scholar
  6. Berke G (1989): The cytolytic T lymphocyte and its mode of action. Immunol Lett 20:169–178PubMedCrossRefGoogle Scholar
  7. Berridge MJ (1987): Inositol trisphosphate and diacylgycerol: two interacting second messengers. J Biol Chem 56:159–193Google Scholar
  8. Berridge MJ (1990): Calcium oscillations. J Biol Chem 265:9583–9586PubMedGoogle Scholar
  9. Bondy SC, Agrawal AK (1980): The inhibition of cerebral high affinity receptor sites by lead and mercury compounds. Arch Toxicol 46:249–256PubMedCrossRefGoogle Scholar
  10. Carafoli E (1989): Intracellular Ca2+ homeostasis. Annu Rev Biochem 56:395–433CrossRefGoogle Scholar
  11. Caspar M, Florin I, Thelestam M (1987): Calcium and calmodulin in cellular intoxication with Clostridium difficile toxin B. J Cell Physiol 132:168–172PubMedCrossRefGoogle Scholar
  12. Dreyer EB, Kaiser PK, Offerman JT, Lipton SA (1990): HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248:364–367PubMedCrossRefGoogle Scholar
  13. Farrell GC, Duddy SK, Kass GE, Llopis, J, Gahm A, Orrenius S (1990): Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver. J Clin Invest 85:1255–1259PubMedCrossRefGoogle Scholar
  14. Fleckenstein A, Frey M, Fleckenstein-Grün G (1983): Cellular injury by cytosolic calcium overload and its prevention by calcium antagonists — a new principle of tissue protection. In: Mechanisms of Hepatocyte Injury and Death, Keppler D, Popper H, Bianchi L, et al, eds., pp. 321–335. Lancaster: MTP Press LimitedGoogle Scholar
  15. Gunther TE, Pfeiffer DR (1990): Mechanisms by which mitochondria transport calcium. Am J Physiol 258:755–786Google Scholar
  16. Imahori K (1982): Calcium-dependent neutral protease: its characterization and regulation. In: Calcium and Cell Function, Cheung WY, ed., Vol. III. Orlando: Academic PressGoogle Scholar
  17. Jewell SA, Bellomo G, Thor H, Orrenius S, Smith MT (1982): Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis. Science 217:1257–1259PubMedCrossRefGoogle Scholar
  18. Jones DP, McConkey DJ, Nicotera P, Orrenius S (1989): Calcium-activated DNA fragmentation in rat liver nuclei. J Biol Chem 264:6398–6403PubMedGoogle Scholar
  19. Kass GEN, Duddy SK, Moore GA, Orrenius S (1989): Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. J Biol Chem 264:15192PubMedGoogle Scholar
  20. Komulainen H, Bondy SC (1988): Increased free intracellular Ca2+ by toxic agents: an index of potential neurotoxicity? Trends Pharmacol Sci 9:154–156PubMedCrossRefGoogle Scholar
  21. Kure S, Tominaga T, Yoshimoto T, Tada K, Narisawa K (1991): Glutumate triggers internucleosomal DNA cleavage in neuronal cells. Biochem Biophys Res Commun 179:39–45PubMedCrossRefGoogle Scholar
  22. Lehninger AL, Vercesi A, Bababunmi EA (1978): Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. Proc Natl Acad Sci USA 75:1690–1694PubMedCrossRefGoogle Scholar
  23. Manev H, Costa E, Wroblewski JT, Guidotti A (1990): Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity. FASEB J 4:2789–2797PubMedGoogle Scholar
  24. McConkey DJ, Chow SC, Orrenius S, Jondal M (1990): NK cell-induced cytotoxicity is dependent on a Ca2+ increase in the target. FASEB 7 4:2661–2664Google Scholar
  25. McConkey DJ, Hartzell P, Duddy SK, Håkansson H, Orrenius S (1988): 2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science 242:256–258PubMedCrossRefGoogle Scholar
  26. McConkey DJ, Nicotera P, Hartzell P, Bellomo G, Wyllie AH, Orrenius S (1989): Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys 269:365–370PubMedCrossRefGoogle Scholar
  27. Mirabelli F, Salis A, Vairetti M, Bellomo G, Thor H, Orrenius S (1989): Cytoskeletal alterations in human platelets exposed to oxidative stress are mediated by oxidative and Ca2+-dependent mechanisms. Arch Biochem Biophys 270:478–488PubMedCrossRefGoogle Scholar
  28. Moore GA, Jewell SA, Bellomo G, Orrenius S (1983): On the relationship between Ca2+ efflux and membrane damage during tert-buiyl hydroperoxide metabolism by liver motochondira. FEBS Lett 153:289–292PubMedCrossRefGoogle Scholar
  29. Nicotera P, McConkey DJ, Jones DP, Orrenius S (1989a): ATP stimulates Ca2+ uptake and increases the free Ca2+ concentration in isolated liver nuclei. Proc Natl Acad Sci USA 86:453–57PubMedCrossRefGoogle Scholar
  30. Nicotera P, Rundgren M, Porubek DJ, Cotgreave I, Moldeus P, Orrenius S, Nelson SD (1989b): On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes. Chem Res Toxicol 2:46–50PubMedCrossRefGoogle Scholar
  31. Nicotera P, Bellomo G, Orrenius S (1990a): The role of Ca2+ in cell killing. Chem Res Toxicol 3:484–494PubMedCrossRefGoogle Scholar
  32. Nicotera P, Orrenius S, Nilsson T, Berggren P-O (1990b): An inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in liver nuclei. Proc Natl Acad Sci USA 87:6858–6862PubMedCrossRefGoogle Scholar
  33. Orrenius S, McConkey DJ, Bellomo G, Nicotera P (1989): Role of Ca2+ in toxic cell killing. Trends Pharmacol Sci 10:281–285PubMedCrossRefGoogle Scholar
  34. Phelps PC, Smith MW, Trump BF (1989): Cytosolic ionized calcium and bleb formation after acute cell injury of cultured rabbit renal tubule cells. Lab Invest 60:630–642PubMedGoogle Scholar
  35. Rossi AD, Larsson O, Manzo L, Orrenius S, Vahter M, Berggren P-O, Nicotera P (1993): Modifications of Ca2+ signalling by inorganic mercury in PC 12 cells. FASEB J 7:1507:1514Google Scholar
  36. Schanne FAX, Kane AB, Young EE, Farber JL (1979): Calcium dependence of toxic cell death: a final common pathway. Science 206:700–702PubMedCrossRefGoogle Scholar
  37. Somylo AP, Bond M, Somylo AV (1985): Calcium content of mitochondria and endoplasmic reticulum in liver frozen rapidly in vivo. Nature 314:622–625CrossRefGoogle Scholar
  38. Van Kuijk FJGM, Sevanian A, Handleman GJ, Dratz EA (1991): A new role for phospholipase A2: protection of membrane from lipid peroxidation damage. Trends Biochem Sci 12:31–34CrossRefGoogle Scholar
  39. Von Burg R, Northington FK, Shamoo A (1980): Methylmercury inhibition of rat brain muscarinic receptors. Toxicol Appl Pharmacol 53:285–292CrossRefGoogle Scholar
  40. Waring P, Eichner RD, Mullbacher A, Sjaarda A (1988): Gliotoxin induced apoptosis in macrophages unrelated to its antiphagocytic properties. Science 263:18493–18499Google Scholar
  41. Woods NM, Cuthbertson KSR, Cobbold PE (1986): Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatozytes. Nature 319:600–602PubMedCrossRefGoogle Scholar
  42. Wyllie AG (1980): Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1994

Authors and Affiliations

  • Sten Orrenius
  • Pierluigi Nicotera

There are no affiliations available

Personalised recommendations