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The role of zinc in caspase activation and apoptotic cell death

  • Ai Q. Truong-Tran
  • Joanne Carter
  • Richard E. Ruffin
  • Peter D. Zalewski
Chapter

Abstract

In addition to its diverse role in many physiological systems, zinc (Zn) has now been shown to be an important regulator of apoptosis. The purpose of this review is to integrate previously published knowledge on Zn and apoptosis with current attempts to elucidate the mechanisms of action of this biometal. This paper begins with an introduction to apoptosis and then briefly reviews the evidence relating Zn to apoptosis. The major focus of this review is the mechanistic actions of Zn and its candidate intracellular targets. In particular, we examine the cytoprotective functions of Zn which suppress major pathways leading to apoptosis, as well as the more direct influence of Zn on the apoptotic regulators, especially the caspase family of enzymes. These two mechanisms are closely related since a decline in intracellular Zn below a critical threshold level may not only trigger pathways leading to caspase activation but may also facilitate the process by which the caspases are activated. Studies by our laboratory in airway epithelial cells show that Zn is co-localized with the precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is critically placed to control apoptosis. Further understanding the different pools of Zn and how they interact with apoptotic pathways should have importance in human disease.

Key words

apoptosis caspase ROS sulfhydryl zinc 

Abbreviations

AEC

Airway epithelial cells

Cu/Zn SOD

Copper zinc superoxide dismutase

z-DEVD-AFC

boc-Asp-Glu-Val-Asp 7-amino-4-trifluoromethyl coumarin

H2O2

Hydrogen peroxide

HNE

Hydroxynonenal

L-NAME

NG-nitro-L-arginine methyl ester

PARP

Poly (ADP-ribose) polymerase

ROS

Reactive oxygen species

TPEN

N,N,N′,N′-tetrakis-2-pyridylmethyl-ethylenediamine

Zn

Zinc

References

  1. Adams R, Ruffin R, Wakefield M, Campbell D, Smith B. 1997 Asthma prevalence, morbidity and management practices in South Australia, 1992–1995. Aust N Z J Med 27, 672–679.PubMedGoogle Scholar
  2. Ahn YH, Kim YH, Hong SH, Koh JY. 1998 Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture. Exp Neurol 154, 47–56.PubMedGoogle Scholar
  3. Aiuchi T, Mihara S, Nakaya M, Masuda Y, Nakajo S, Nakaya K. 1998 Zinc ions prevent processing of caspase-3 during apoptosis induced by geranylgeraniol in HL-60 cells. J Biochem (Tokyo) 124, 300–303.Google Scholar
  4. Banan A, Fields JZ, Decker H, Zhang Y, Keshavarzian A. 2000 Nitric oxide and its metabolites mediate ethanol-induced micro-tubule disruption and intestinal barrier dysfunction. J Pharmacol Exp Ther 294, 997–1008.PubMedGoogle Scholar
  5. Barbieri D, Troiano L, Grassilli E, Agnesini C, Cristofalo EA, Monti D, Capri M, Cossarizza A, Franceschi C. 1992 Inhibition of apoptosis by zinc: a reappraisal. Biochem Biophys Res Commun 187, 1256–1261.PubMedGoogle Scholar
  6. Berendji D, Kolb-Bachofen V, Meyer KL, Grapenthin O, Weber H, Wahn V, Kröncke KD. 1997 Nitric oxide mediates intracytoplasmie and intranuclear zinc release. FEBS Lett 405, 37–41.PubMedGoogle Scholar
  7. Bettger WJ, O’Dell BL. 1981 A critical physiological role of zinc in the structure and function of biomembranes. Life Sci 28, 1425–1438.PubMedGoogle Scholar
  8. Blagosklonny MV, Wu GS, Omura S, el-Deiry WS. 1996 Proteasome-dependent regulation of p2lwafil/cipl expression. Biochem Biophvs Res Commun 227, 564–569.Google Scholar
  9. Cain K, Brown DG, Langlais C, Cohen GM. 1999 Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex. J Biol Chem 274, 22686–22692.PubMedGoogle Scholar
  10. Chai F, Truong-Tran AQ, Ho LH, Zalewski PD. 1999 Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol Cell Biol 77, 272–278.PubMedGoogle Scholar
  11. Chai F, Truong-Tran AQ, Evdokiou, A Young GP, Zalewski PD. 2000 Intracellular Zinc Depletion Induces Caspase Activation and p2lwafl/Cipl Cleavage in Human Epithelial Cell Lines. J Infect Diseases 182, S85–S92.Google Scholar
  12. Chautan M, Chazal G, Cecconi F, Gruss P, Golstein P. 1999 Interdigital cell death can occur through a necrotic and caspaseindependent pathway. Curr Biol 9, 967–970.PubMedGoogle Scholar
  13. Cohen JJ, Duke RC. 1984 Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 132, 38–42.PubMedGoogle Scholar
  14. Cohen G, Sun X-M, Snowden RT, Dinsdale D, Skilleter DN. 1992 Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J 286, 331–334.PubMedGoogle Scholar
  15. Cui L, Takagi Y, Wasa M, Sando K, Khan J, Okada A. 1999 Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats. J Nutr 129, 792–798.PubMedGoogle Scholar
  16. Cui L, Takagi Y, Sando K, Wasa M, Okada A. 2000 Nitric oxide synthase inhibitor attenuates inflammatory lesions in the skin of zinc-deficient rats. Nutrition 16, 34–41.PubMedGoogle Scholar
  17. Da Silva JJRF, Williams. RJP: 1991 Zinc: Lewis acid catalysis and regulation. In: Williams, RJP ed. The Biological Chemistry of the Elements. Oxford, UK: Clarendon Press: 299–318.Google Scholar
  18. Dimmeler S, Haendeler J, Galle J, Zeiher AM. 1997 Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the `response to injury’ hypothesis. Circulation 95, 1760–1763.PubMedGoogle Scholar
  19. Toro R, Galdo CG, Gialanella G, Miraglia DE, Giudice M, Moro R, Perrone L. 1987 Zinc and copper status of allergic children. Acta Paediatr Scand 76, 612–6I7.Google Scholar
  20. Duvall E, Wyllie AH. 1986 Death and the cell. Immunol Today 7, 115–119.Google Scholar
  21. Earnshaw WC, Martins LM, Kaufmann SH. 1999 Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68, 383–424.PubMedGoogle Scholar
  22. Kholy MS, Gas Allah MA, el-Shimi S, el-Baz F, el-Tayeb H, Abdel-Hamid MS. 1990 Zinc and copper status in children with bronchial asthma and atopic dermatitis. J Egypt Public Health Assoc 65, 657–668.PubMedGoogle Scholar
  23. Esposti MD, Hatzinisiriou I, McLennan H, Ralph S. 1999 Bel-2 and mitochondria) oxygen radicals. New approaches with reactive oxygen species-sensitive probes. J Biol Chem 274, 29831–29837.PubMedGoogle Scholar
  24. Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. 1997 Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J 16, 2271–2281.PubMedGoogle Scholar
  25. Floersheim GL, Christ A, Koenig R, Racine C, Gudat F. 1992 Radiation-induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and WR 2721. Int J Cancer 52, 604–608.PubMedGoogle Scholar
  26. Frade JM, Michaelidis TM. 1997 Origin of eukaryotic programmed cell death: a consequence of aerobic metabolism? Bioessays 19, 827–832.PubMedGoogle Scholar
  27. Fraker PJ, Telford WG. 1997 A reappraisal of the role of zinc in life and death decisions of cells. Proc Soc Exp Biol Med 215, 229–236.PubMedGoogle Scholar
  28. Frederickson CJ. 1989 Neurobiology of zinc and zinc-containing neurons. In! Rev Neurobiol 31, 145–238.Google Scholar
  29. Fujita N, Nagahashi A, Nagashima K, Rokudai S, Tsuruo T. 1998 Acceleration of apoptotic cell death after the cleavage of Bel-XL protein by caspase-3-like proteases. Oncogene 17, 1295–1304.PubMedGoogle Scholar
  30. Fukamachi Y, Karasaki Y, Sugiura T, Itoh H, Abe T, Yamamura K, Higashi K. 1998 Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the BcI-2/Bax ratio. Biochem Biophys Res Commun 246, 364–369.PubMedGoogle Scholar
  31. Ghibelli L, Coppola S, Fanelli C, Rotilio G, Civitareale P, Scovassi Al, Ciriolo MR. 1999 Glutathione depletion causes cytochrome c release even in the absence of cell commitment to apoptosis. FASEB J 13, 2031–2036.PubMedGoogle Scholar
  32. Grutter MG. 2000 Caspases: key players in programmed cell death. Curr Opin Struct Biol 10, 649–55.PubMedGoogle Scholar
  33. Halliwell B. 1991 Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91, 14S–22S.PubMedGoogle Scholar
  34. Hamatake M, Iguchi K, Hirano K, Ishida R. 2000 Zinc Induces Mixed Types of Cell Death, Necrosis, and Apoptosis, in Molt-4 Cells. J Biochem (Tokyo) 128, 933–939.Google Scholar
  35. Hennig B, Wang Y, Ramasamy S, McClain CJ. 1992 Zinc deficiency alters barrier function of cultured porcine endothelial cells. J Nutr 122, 1242–1247.PubMedGoogle Scholar
  36. Hennig B, McClain CJ, Diana JN. 1993 Function of vitamin E and zinc in maintaining endothelial integrity. Implications in atherosclerosis. Ann NYAcad Sci 686, 99–109.Google Scholar
  37. Hennig B, Meerarani P, Ramadass P, Toborek M, Malecki A, Slim R, McClain CJ. 1999. Zinc nutrition and apoptosis of vascular endothelial cells: implications in atherosclerosis. Nutrition 15, 744–748.PubMedGoogle Scholar
  38. Hesketh JE. 1982. Zinc-stimulated microtubule assembly and evi- dence for zinc binding to tubulin. Int J Biochem 14, 983–990.PubMedGoogle Scholar
  39. Jacotot E, Costantini P, Laboureau E, Zamzami N, Susin SA, Kroemer G. 1999 Mitochondria) membrane permeabilization during the apoptotic process. Ann NYAcad Sci 887, 18–30.Google Scholar
  40. Janicke RU, Sprengart ML, Wati MR, Porter AG. 1998 Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273, 9357–9360.PubMedGoogle Scholar
  41. Jankowski-Hennig MA, Clegg MS, Daston GP, Rogers JM, Keen CL. 2000 Zinc-deficient rat embryos have increased caspase alike activity and apoptosis. Biochem Biophys Res Commun 271, 250–256.PubMedGoogle Scholar
  42. Kadrabova J, Mad’aric A, Podivinsky F, Gazdik F, Ginter F. 1996 Plasma zinc, copper and copper/zinc ratio in intrinsic asthma. J Trace Elem Med Biol 10, 50–53.PubMedGoogle Scholar
  43. Kerr JFR, Searle J, Harmon BV, Bishop CJ. 1987 Apoptosis. In: Potten CS. ed. Perspectives of Mammalian Cell Death. Oxford, UK: Oxford Uni. Press: 93–128.Google Scholar
  44. King KL, Cidlowski JA. 1998 Cell cycle regulation and apoptosis. Annu Rev Physiol 60, 601–617.PubMedGoogle Scholar
  45. Kolenko V, Uzzo RG, Bukowski R, Bander NH, Novick AC, His ED, Finke JH. 1999 Dead or dying: necrosis versus apoptosis in caspase-deficient human renal cell carcinoma. Cancer Res 59, 2838–2842.PubMedGoogle Scholar
  46. Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. 1993 Bel2/Bax: a rheostat that regulates an antioxidant pathway and cell death. Semin Cancer Biol 4, 327–332.PubMedGoogle Scholar
  47. Kown MH, Van Der Steenhoven T, Blankenberg FG, Hoyt G, Berry GJ, Tait JF, Strauss HW, Robbins RC. 2000 Zinc-mediated reduction of apoptosis in cardiac allografts. Circulation 102 (Suppl 3), 228–232.Google Scholar
  48. Krajewska M, Wang HG, Krajewski S, Zapata JM, Shabaik A, Gascoyne R, Reed JC. 1997 Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer Res 57, 1605–1613.PubMedGoogle Scholar
  49. Kraus A, Roth HP, Kirchgessner M. 1997 Supplementation with vitamin C, vitamin E or beta-carotene influences osmotic fragility and oxidative damage of erythrocytes of zinc-deficient rats. J Nutr 127, 1290–1296.Google Scholar
  50. Krebs JF, Srinivasan A, Wong AM, Tomaselli KJ, Fritz LC, Wu JC. 2000 Heavy membrane-associated caspase 3: Identification, isolation, and characterization. Biochemistry 39, 16056–16063.PubMedGoogle Scholar
  51. Kroemer G. 1998 The mitochondrion as an integrator/coordinator of cell death pathways. Cell Death Differ 5, 547.PubMedGoogle Scholar
  52. Kroemer G, Reed JC. 2000 Mitochondrial control of cell death. Nat Med 6, 513–519.PubMedGoogle Scholar
  53. Kuo IC, Seitz B, LaBree L, McDonnell PJ. 1997 Can zinc prevent apoptosis of anterior keratocytes after superficial keratectomy? Cornea 16, 550–555.PubMedGoogle Scholar
  54. Laitinen A, Laitinen LA. 1994 Airway morphology: epithelium/basement membrane. Am J Respir Crit Care Med 150, S14–SI7.Google Scholar
  55. Lazebnik YA, Cole S, Cooke CA, Nelson WG, Earnshaw WC. 1993 Nuclear events of apoptosis in vitro in cell-free mitotic extracts: A model system for analysis of the active phase of apoptosis. J Cell Biol 123, 7–22.PubMedGoogle Scholar
  56. Liebler DC. 1993 The role of metabolism in the anti-oxidant function of vitamin E. Crit Rev Toxicol 23, 147–169.Google Scholar
  57. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. 1996 Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147–157.PubMedGoogle Scholar
  58. Longin AS, Mezin P, Favier A, Verdetti J. 1997 Presence of zinc and calcium permeant channels in the inner membrane of the nuclear envelope. Biochem Biophys Res Commun 235, 236–241.PubMedGoogle Scholar
  59. Maret W, Jacob C, Vallee BL, Fischer EH. 1999 Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc Natl Acad Sci USA 96, 1936–1940.PubMedGoogle Scholar
  60. Martin SJ, Cotter TG. 1990 Specific loss of microtubules in HL- 60 cells leads to programmed cell death (apoptosis). Biochem Soc Trans 18, 299–301.PubMedGoogle Scholar
  61. Martin SJ, Mazdai G, Strain JJ, Cotter TG, Hannigan BM. 1991 Programmed cell death (apoptosis) in lymphoid and myeloid cell lines during zinc deficiency. Clin Exp Immunol 83, 338–343.PubMedGoogle Scholar
  62. Matsushita K, Kitagawa K, Matsuyama T, Ohtsuki T, Taguchi A, Mandai K, Mabuchi T, Yagita Y, Yanagihara T, Matsumoto M. 1996 Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus. Brain Res 743, 362–365.PubMedGoogle Scholar
  63. Meerarani P, Ramadass P, Toborek M, Bauer HC, Bauer H, Hennig B. 2000 Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha. Am J Clin Nutr71, 81–87.Google Scholar
  64. Mesner PW, Bible KC, Martins LM, Kottke TJ, Srinivasula SM, Svingen PA, Chilcote TJ, Basi GS, Tung JS, Krajewski S, Reed JC, Alnemri ES, Earnshaw WC, Kaufmann SH. 1999 Characterization of caspase processing and activation in HL-60 cell cytosol under cell-free conditions. Nucleotide requirement and inhibitor profile. J Biol Chem 274, 22635–22645.PubMedGoogle Scholar
  65. Mills PR, Davies RI, Devalia JL. 1999 Airway epithelial cells, cytokines, and pollutants. Am J Respir Crit Care Med 160, 538–543.Google Scholar
  66. Nakatani T, Tawaramoto M, Opare Kennedy D, Kojima A, MatsuiYuasa I. 2000 Apoptosis induced by chelation of intracellular zinc is associated with depletion of cellular reduced glutathione level in rat hepatocytes. Chem Biol Interact 125, 151–163.PubMedGoogle Scholar
  67. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Mun-day A, Raju SM, Smulson E, Yamin T-T, Yu VL, Miller DK. 1995 Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature (Lond) 376, 37–43.Google Scholar
  68. Nickolson VJ, Veldstra H. 1972 The influence of various cations on the binding of colchicine by rat brain homogenates. Stabilization of intact neurotubules by zinc and cadmium ions. FEBS Lett 23, 309–314.PubMedGoogle Scholar
  69. Okuno S, Shimizu S, Ito T, Nomura M, Hamada E, Tsujimoto Y, Matsuda H. 1998 Bcl-2 prevents caspase-independent cell death. J Biol Chem 273, 34272–34277.PubMedGoogle Scholar
  70. Oteiza PI, Olin KL, Fraga CG, Keen CL. 1995 Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr 125, 823–829.PubMedGoogle Scholar
  71. Oteiza PI, Olin KL, Fraga CG, Keen CL. 1996 Oxidant defense systems in testes from zinc-deficient rats. Proc Soc Exp Biol Med 213, 85–91.PubMedGoogle Scholar
  72. Oteiza PI, Clegg MS, Zaga MP, Keen CL. 2000 Zinc deficiency induces oxidative stress and AP- I activation in 3T3 cells. Free Radic Biol Med 28, 1091–1099.PubMedGoogle Scholar
  73. Palmiter RD, Cole TB, Findley SD. 1996 ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO J 15, 1784–1791.PubMedGoogle Scholar
  74. Parat MO, Richard MJ, Beani JC, Favier A. 1997 Involvement of zinc in intracellular oxidant/anti-oxidant balance. Biol Trace Elern Res 60, 187–204.Google Scholar
  75. Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Porier GG, Hannun YA. 1997 Zinc is a potent inhibitor of the apoptotic protease caspase-3. A novel target for zinc in the inhibition of apoptosis. J Biol Chem 272, 18530–18533.PubMedGoogle Scholar
  76. Pham CT, Thomas DA, Mercer JD, Ley TJ. 1998 Production of fully active recombinant murine granzyme B in yeast. J Biol Chem 273, 1629–1633.PubMedGoogle Scholar
  77. Powell SR. 2000 The antioxidant properties of zinc. J Nutrition 130, 14475–1454S.Google Scholar
  78. Reed JC, Jurgensmeier JM, Matsuyama S. 1998 Bcl-2 family pro- teins and mitochondria. Biochim Biophvs Acta 1366, 127–137.Google Scholar
  79. Rogers JM, Taubeneck MW, Daston GP, Sulik KK, Zucker RM, El-stein KH, Jankowski MA, Keen CL. 1995 Zinc deficiency causes apoptosis but not cell cycle alterations in organogenesis-stage rat embryos: effect of varying duration of deficiency. Teratology 52, 149–159.PubMedGoogle Scholar
  80. Rossig L, Fichtlscherer B, Breitschopf K, Haendeler J, Zeiher AM, Mulsch A. Dimmeler S. 1999 Nitric oxide inhibits caspase-3 by S-nitrosation in vivo. J Biol Chem 274, 6823–6826.PubMedGoogle Scholar
  81. Roychowdhury M, Sarkar N, Manna T, Bhattacharyya S, Sarkar T, Basusarkar P, Roy S, Bhattacharyya B. 2000 Sulfhydryls of tubulin. A probe to detect conformational changes of tubulin. Eur J Biochem 267, 3469–3476.PubMedGoogle Scholar
  82. Salas PJ. 1999 Insoluble gamma-tubulin-containing structures are anchored to the apical network of intermediate filaments in polarized CACO-2 epithelial cells. J Cell Biol 146, 645–658.PubMedGoogle Scholar
  83. Sen CK, Sashwati R, Packer L. 1999 Fas mediated apoptosis of human Jurkat T-cells: intracellular events and potentiation by redox-active alpha-lipoic acid. Cell Death Differ 6, 481–491.PubMedGoogle Scholar
  84. Sensi SL, Yin HZ, Carriedo SG, Rao SS, Weiss JH. 1999 Preferential Zn2+ influx through Cat+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc Natl Acad Sci USA 96, 2414–2419.PubMedGoogle Scholar
  85. Seve M, Favier A, Osman M, Hernandez D, Vaitaitis G, Flores NC, McCord JM, Flores SC. 1999 The human immunodeficiency virus-1 tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Spl DNA binding in HeLa cells. Arch Biochem Biophvs 361, 165–172.Google Scholar
  86. Song Z, Steller H. 1999 Death by design: mechanism and control of apoptosis. Trends Cell Biol 9, 49–52.Google Scholar
  87. Stennicke HR, Salvesen GS. 1997 Biochemical characteristics of caspases-3, -6, -7, and -8. J Biol Chem 272, 25719–25723.PubMedGoogle Scholar
  88. Strasser A, O’Connor L, Dixit VM. 2000 Apoptosis signaling. Annu Rev Biochem 69, 217–245.PubMedGoogle Scholar
  89. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. 1999 Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 274, 5053–5060.PubMedGoogle Scholar
  90. Sunderman FW. 1995 The influence of zinc on apoptosis. Ann Clin Lab Sci 25, 134–142.PubMedGoogle Scholar
  91. Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC. 1996 Cleavage of lamm A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis. Proc Natl Acad Sci USA 93, 8395–8400.PubMedGoogle Scholar
  92. Taylor CG, Towner RA, Janzen EG, Bray TM. 1990 MRI detection of hyperoxia-induced lung edema in Zn deficient rats. Free Radic Biol Med 9, 229–233.PubMedGoogle Scholar
  93. Taylor CG, McCutchon TL, Boermans H, DiSilvestro RA, Bray TM. 1997 Comparison of Zn and vitamin E for protection against hyperoxia-induced lung damage. Free Radie Biol Med 22, 543–550.Google Scholar
  94. Thompson CB. 1995 Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462.PubMedGoogle Scholar
  95. Thornberry NA, Lazebnik Y. 1998 Caspases: enemies within. Science 281, 1312–1316.PubMedGoogle Scholar
  96. Treves S, Trentini PL, Ascanelli M, Bucci G, Di Virgilio F. 1994 Apoptosis is dependent on intracellular zinc and independent of intracellular calcium in lymphocytes. Exp Cell Res 211, 339–343.PubMedGoogle Scholar
  97. Truong-Tran AQ, Ruffin RE, Zalewski PD. 2000a Visualization of labile zinc and its role in apoptosis of primary airway epithelial cells and cell lines. Am J Physiol 279, L1172–L1183.Google Scholar
  98. Truong-Tran AQ, Ho LH, Chai F, Zalewski PD. 2000b Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J Nutrition 130 (Suppl), 1459S–1466S.Google Scholar
  99. Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD. 2001 New Insights Into The Role of Zinc in The Respiratory Epithelium. Immunol Cell Biol79, 170–177.Google Scholar
  100. Tsutsui Y, Nakamura Y, Yamaguchi S, Kawanaka N, Sato M. 1999 Effects of zinc acexamate (NAS-501) on superoxide radicals and lipid peroxidation of rat gastric mucosa. Pharmacology 58, 209–219.PubMedGoogle Scholar
  101. Untergasser G, Rumpold H, Plas E, Witkowski M, Pfister G, Berger P. 2000 High Levels of Zinc Ions Induce Loss of Mitochondrial Potential and Degradation of Anti-apoptotic Bel-2 Protein in in vitro Cultivated Human Prostate Epithelial Cells. Biochem Biophys Res Commun 279, 607–614.PubMedGoogle Scholar
  102. Vallee BL, Falchuk KH. 1993 The biochemical basis of zinc physiology. Physiol Rev 73, 79–118.PubMedGoogle Scholar
  103. Vatassery GT. 1992 Vitamin E. Neurochemistry and implications for neurodegeneration in Parkinson’s disease. Ann NYAcad Sci 669, 97–109.Google Scholar
  104. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer S.I. 1993 Bel2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75, 229–240.PubMedGoogle Scholar
  105. Waring P, Egan M, Braithwaite A, Mullbacher A, Sjaarda A. 1990 Apoptosis induced in macrophages and T blasts by the mycotoxin sporidesmin and protection by Zn2+ salts. Int J Immunopharmac 12, 445–457.Google Scholar
  106. Williams RJP. 1987 The biochemistry of zinc. Polyhedron 6, 61–69.Google Scholar
  107. Wolf CM, Eastman A. 1999 The temporal relationship between protein phosphatase, mitochondrial cytochrome c release, and caspase activation in apoptosis. Exp Cell Res 247, 505–513.PubMedGoogle Scholar
  108. Wyllie AH. 1997 Apoptosis: an overview. Br Med Bull 53, 451–465. Zalewski PD, Forbes IJ, Giannakis C, Cowled PA, Betts WH. 1990 Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton. FEBSLett 273, 131–134.Google Scholar
  109. Zalewski PD, Forbes IJ, Giannakis C. 1991 Physiological role for zinc in prevention of apoptosis (gene-directed death). Biochem Inter 24, 1093–1101.Google Scholar
  110. Zalewski PD, Forbes IJ. 1993 Intracellular zinc and the regulation of apoptosis. In: Lavin M, Watters D. eds. Programmed Cell Death: The Cellular and Molecular Biology of Apoptosis. Melbourne: Harwood Academic Publishers: 73–86.Google Scholar
  111. Zalewski PD, Forbes IJ, Betts WH. 1993 Correlation of apoptosis with change in intracellular labile Zn, using Zinquin, a new specific fluorescent probe for zinc. Biochem J 296, 403–408.PubMedGoogle Scholar
  112. Zalewski PD, Millard SH, Forbes IJ, Kapaniris O, Slavotinek A, Betts WH. 1994a Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc. J Histochem Cytochem 42, 877–884.PubMedGoogle Scholar
  113. Zalewski PD, Forbes IJ, Seamark RF, Borlinghaus R, Betts WH, Lincoln SF, Ward AD. 1994b Flux of intracellular labile zinc during apoptosis (gene-directed cell death) revealed by a specific chemical probe, Zinquin. Chem Biol 1, 153–161.PubMedGoogle Scholar
  114. Zalewski PD, Jian X, Soon LLL, Breed WG, Seamark RF, Lincoln SF, Ward AD, Sun F-Z. 1996 Changes in distribution of labile zinc in mouse spermatozoa during maturation in the epididymis assessed by the fluorophore Zinquin. Reprod Fertil Develop 8, 1097–1105.Google Scholar
  115. Zamzami N, Susin SA, Marchetti P, Hirsch T, Gomez-Monterrey I, Castedo M, Kroemer G. 1996 Mitochondrial control of nuclear apoptosis. J Exp Med 183, 1533–1544.PubMedGoogle Scholar
  116. Zhivotovsky B, Samali A, Gahm A, Orrenius S. 1999 Caspases: their intracellular localization and translocation during apoptosis. Cell Death Differ 6, 644–651.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Ai Q. Truong-Tran
    • 1
  • Joanne Carter
    • 1
  • Richard E. Ruffin
    • 1
  • Peter D. Zalewski
    • 1
  1. 1.Department of MedicineUniversity of Adelaide, The Queen Elizabeth HospitalWoodvilleAustralia

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