Acta Med. 2007, 50: 43-49

Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury

Emil Rudolf

Charles University in Prague, Faculty of Medicine in Hradec Králové, Department of Medical Biology and Genetics, Hradec Králové, Czech Republic

Received November 1, 2006
Accepted January 1, 2007


1. Bae SN, Lee, YS, Kim MY, Kim JD, Park LO. Antiproliferrative and apoptotic effects of zinc-citrate compound (CIZAR®) on human epithelial ovarian cancer cell line, OVCAR-3. Gynecol Oncol 2006; 103: 127–36. <>
2. Chen W, Wang Z, Zhang Y. The effect of zinc on the apoptosis of cultured human retinal pigment epithelial cells. J Huazhong Univ Sci Technolog Med Sci 2003; 23: 414–17.
3. Dineley KE, Votjakova TV, Reynolds IJ. Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration. J Nerochem 2003; 85: 563–70. <>
4. Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 2004; 16: 663–69. <>
5. Feng P, Li TL, Guan ZX, Franklin RB, Costello LC. Direct effect of zinc on mitochondrial apoptogenenesis in prostate cells. Prostate 2002; 52: 311–18. <> <PubMed>
6. Fong LY, Nguyen VT, Farber JL. Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc. J Natl Cancer Inst 2001; 93: 1525–33. <>
7. Fraker PJ, Telford WG. A reappraisal of the role of zinc in life and death decisions of cells. Proc Soc Exp Biol Med 1997; 215: 229–236. <>
8. Frederickson CJ, Suh SW, Silva D, Thompson RB. Importance of zinc in the central nervous system: the zinc-containing neuron. J Nutr 2000; 130: 1471S-83S. <>
9. Haase H, Beyersmann D. Intracellular zinc distribution and transport in C6 rat glioma cells. Biochem Biophys Res Commun 2002; 296: 923–28. <>
10. Hamatake M, Iguchi K, Hirano K, Ishida R. Zinc induces mixed types of cell death, necrosis, and apoptosis, in molt-4 cells. J Biochem (Tokyo) 2000; 128: 933–39. <>
11. Iitaka M, Kakinuma S, Fujimaki S, Posuta I, Fujita T, Yamanaka K, Wada S, Katayama S. Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines. J Endocrinol 2001; 169:417–24. <>
12. Kim YH, Kim EY, Gwag BJ, Sohn S, Koh JY. Zinc-induced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals. Neuroscience 1999; 89: 175–82. <>
13. Kim YH, Koh JY. The role of NADPH oxidase and neuronal nitric oxide synthase n zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture. Exp Neurol 2002; 177: 407–418. <>
14. Kondoh M, Tasaki E, Araragi S, Takiguchi M, Higashimoto M, Watanabe Y, Sato M. Requirement of caspase and p38MAPK activation in zinc-induced apoptosis in human leukemia HL-60 cells. Eur J Biochem 2002; 269: 6204–11. <>
15. Maret W, Vallee BL. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc natl Acad Sci USA 1998; 95: 3478–82. <> <PubMed>
16. Matsunaga Y, Kawai Y, Kohda Y, Gemba M. Involvement of activation of NADPH oxidase and extracellular signal-regulated kinase (ERK) in renal cell injury induced by zinc. J Toxicol Sci 2005; 30: 135–44. <>
17. Niida H, Nakanishi M. DNA damage checkpoints in mammals. Mutagenesis 2006; 21: 3–9. <>
18. Papucci L, Formigli L, Schiavone N, Tani A, Donnini M, Lapucci A, Perna F, Tempestini A, Witort E, Morganti M, Nosi D, Orlandini GE, Zecchi Orlandini S, Capaccioli S. Apoptosis shifts to necrosis via intermediate types of cell death by a mechanism depending on c-myc and bcl-2 expression. Cell Tissue Res 2004; 316: 197–209. <>
19. Provinciali M, Donnini A, Argentati K, Di Stasio G, bartozzi B, Bernardini G. Reactive oxygen species modulate Zn (2+)-induced apoptosis in cancer cells. Free Radical Biology & Medicine 2002; 32: 431–45. <>
20. Rudolf E, Červinka M. Cytoskeletal changes in non-apoptotic cell death. Acta Medica (Hradec Králové) 2006; 49: 123–28. <>
21. Rudolf E, Červinka M, Cerman J. Zinc has ambiguous effects on chromium (VI)-induced oxidative stress and apoptosis. J Trace Elem Med Biol 2005; 18: 251–60. <>
22. Sauer GR, Smith Dm, Cahalane M, Wu LN, Wuthier RE. Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes. J Cell Biochem 2003; 88: 954–69. <>
23. Suh SW, Jensen KB, Jensen MS, Silva DS, Kesslak PJ, Danscher G, Frederickson CJ. Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer’s diseased brains. Brain Res 2000; 852: 274–278. <>
24. Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z. Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants. Cell cycle 2006; 5: 1940–45. <> <PubMed>
25. Tapiero H, Tew KD. Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Parmacother 2003; 57: 399–411. <>
26. Truong-tran AQ, Ho LH, Chai F, Zalewski PD. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J Nutr 2000; 130: 1459S-66S. <>
27. Wiseman DA, Wells SM, Wilham J, Hubbard M, Welker JE, Bůack SM. Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression. Am J Physiol Cell Physiol 2006; 291: C555–68. <>
28. Ziegler U, Groscurth P. Morphological features of cell death. News Physiol Sci 2004; 19: 124–28.
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