The effect of zinc and the role of p53 in copper-induced cellular stress responses

Journal of Applied Toxicology

Volumn 33, Issue 7, 2013, Pages 527-536

  Formigari, Alessia ^a   Gregianin, Elisa ^a   Irato, Paola ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Apoptosis; Cancer; Caspase; Metallothionein; Reactive oxygen species; Wilson's disease

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CASPASE 3; CASPASE 6; CASPASE 9; COPPER; COPPER ZINC SUPEROXIDE DISMUTASE; CYTOCHROME C; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; METALLOTHIONEIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P53; REACTIVE OXYGEN METABOLITE; ZINC;

APOPTOSIS; ARTICLE; BINDING SITE; CANCER RADIOTHERAPY; CARCINOGENESIS; CELL CYCLE PROGRESSION; CELL GROWTH; CELLULAR STRESS RESPONSE; CHROMOSOME ABERRATION; DNA DAMAGE; DNA REPLICATION; DOWN REGULATION; ENZYME ACTIVITY; EUKARYOTIC CELL; GENE ACTIVATION; GENE EXPRESSION; HUMAN; MISSENSE MUTATION; MITOGENESIS; NONHUMAN; NONSENSE MUTATION; OXIDATION; OXIDATIVE STRESS; PATHOGENESIS; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN STABILITY; PROTEIN STRUCTURE; RESPIRATORY CHAIN; SIGNAL TRANSDUCTION; TUMOR RESISTANCE; WILSON DISEASE;

ANIMALS; COPPER; GENES, P53; HEPATOLENTICULAR DEGENERATION; HUMANS; METALLOTHIONEIN; OXIDATIVE STRESS; RADIOTHERAPY; TUMOR SUPPRESSOR PROTEIN P53; ZINC;

RATTUS;

EID: 84878190233     PISSN: 0260437X     EISSN: 10991263     Source Type: Journal    
DOI: 10.1002/jat.2854     Document Type: Article

References (110)

1. 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. 124: 300-303.
2. Akaike T, Maeda H. 2000. Nitric oxide and virus infection. Immunology 101: 300-308.
3. Anaganti S, Fernández-Cuesta L, Langerød A, Hainaut P, Olivier M. 2011. p53-Dependent repression of focal adhesion kinase in response to estradiol in breast cancer cell-lines. Cancer Lett. 300: 215-224.
4. Apelgot S, Coppey J, Fromentin A, Guille E, Poupon MF, Roussel A. 1986. Altered distribution of copper (64Cu) in tumor-bearing mice and rats. Anticancer Res. 6: 159-164.
5. Azevedo MM, Almeida B, Ludovico P, Cássio F. 2009. Metal stress induces programmed cell death in aquatic fungi. Aquat. Toxicol. 92: 264-270.
6. Bao B, Prasad AS, Beck FW, Snell D, Suneja A, Sarkar FH, Doshi N, Fitzgerald JT, Swerdlow P. 2008. Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients. Transl. Res. 152: 67-80.
7. Begley TJ, Samson LD. 2004. Network responses to DNA damaging agents. DNA Repair 3: 1123-1132.
8. Besser L, Chorin E, Sekler I, Silverman WF, Atkin S, Russell JT, Hershfinkel M. 2009. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J. Neurosci. 29: 2890-2901.
9. Beyersmann D, Haase H. 2001. Functions of zinc in signalling, proliferation and differentiation of mammalian cells. Biometals 14: 331-341.
10. Bopp SK, Abicht HK, Knauer K. 2008. Copper-induced oxidative stress in rainbow trout gill cells. Aquat. Toxicol. 86: 197-204.
11. Cardoso SV, Silveira-Junior JB, De Carvalho Machado V, De-Paula AMB, Loyola AM, De Aguiar MCF. 2009. Expression of metallothionein and p53 antigens are correlated in oral squamous cell carcinoma. Anticancer Res. 29: 1189-1194.
12. Cherian MG, Jayasurya A, Bay BH. 2003. Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat. Res. 533: 201-209.
13. Chesters JK, Petrie L, Lipson KE. 1993. Two zinc-dependent steps during G1 to S phase transition. J. Cell. Physiol. 155: 445-451.
14. Chimienti F, Seve M, Richard S, Mathieu J, Favier A. 2001. A role of cellular zinc in programmed cell death: temporal relationship between zinc depletion, activation of caspases, and cleavage of Sp family transcription factors. Biochem. Pharmacol. 62: 51-62.
15. Cohen JJ. 1993. Apoptosis. Immunol. Today 14: 126-130.
16. Cousins RJ, Lee-Ambrose LM. 1992. Nuclear zinc uptake and interactions and metallothionein gene expression are influenced by dietary zinc in rats. J. Nutr. 122: 56-64.
17. Cuanjungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT, Atwood CS, Huang X, Farrag YW, Perry G, Bush AI. 2000. Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of A beta by zinc. J. Biol. Chem. 275: 19439-19442.
18. Del Río MJ, Vélez-Pardo C. 2004. Transition metal-induced apoptosis in lymphocytes via hydroxyl radical generation, mitochondria dysfunction, and caspase-3 activation: an in vitro model for neurodegeneration. Arch. Med. Res. 35: 185-193.
19. Faller P. 2009. Copper and zinc binding to amyloid-β: coordination, dynamics, aggregation, reactivity and metal-ion transfer. Chem. Bio. Chem. 10: 2837-2845.
20. Fang J, Akaike T, Maeda H. 2004. Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis 9: 27-35.
21. Fang J, Nakamura H, Iyer AK. 2007. Tumor-targeted induction of oxystress for cancer therapy. J. Drug Target. 15: 475-486.
22. Fang J, Seki T, Maeda H. 2009. Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Adv. Drug Deliv. Rev. 61: 290-302.
23. Fanzo JC, Reaves SK, Cui L, Zhu L, Wu JYJ. 2001. Zinc status affects p53, gadd45, and c-fos expression and caspase-3 activity in human bronchial epithelial cells. Am. J. Physiol. Cell Physiol. 281: C751-C757.
24. Feng P, Li T, Guan Z, Franklin RB, Costello LC. 2008. The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant prostate cells. Mol. Cancer 7: 25-30.
25. Filomeni G, Cerchiaro G, Da Costa Ferreira AM, De Martino A, Pedersen JZ, Rotilio G, Ciriolo MR. 2007. Pro-apoptotic activity of novel isatin-Schiff base copper(II) complexes depends on oxidative stress induction and organelle-selective damage. J. Biol. Chem. 282: 12010-12021.
26. Fletcher AE. 2010. Free radicals, antioxidants and eye diseases: evidence from epidemiological studies on cataract and age-related macular degeneration. Ophthalmic Res. 44: 191-198.
27. Ford JM. 2005. Regulation of DNA damage recognition and nucleotide excision repair: another role for p53. Mutat. Res. 577: 195-202.
28. Formigari A, Irato P, Santon A. 2007. Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comp. Biochem. Physiol. C 146: 443-459.
29. 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 Bcl-2/Bax ratio. Biochem. Biophys. Res. Commun. 246: 364-369.
30. García-Giménez JL, González-Alvarez M, Liu-González M, Macías B, Borrás J, Alzuet G. 2009. Toward the development of metal-based synthetic nucleases: DNA binding and oxidative DNA cleavage of a mixed copper(II) complex with N-(9H-purin-6-yl)benzenesulfonamide and 1, 10-phenantroline. Antitumor activity in human Caco-2 cells and Jurkat T lymphocytes. Evaluation of p53 and Bcl-2 proteins in the apoptotic mechanism. J. Inorg. Biochem. 103: 923-934.
31. Gazaryan IG, Krasinskaya IP, Kristal BS, Brown AM. 2007. Zinc irreversibly damages major enzymes of energy production and antioxidant defence prior to mitochondrial permeability transition. J. Biol. Chem. 282: 24373-24380.
32. Goldstein I, Marcel V, Olivier M, Oren M, Rotter V, Hainaut P. 2011. Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer Gene Ther. 18: 2-11.
33. Griffitt RJ, Weil R, Hyndman KA, Denslow ND, Powers K, Taylor D, Barber DS. 2007. Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environ. Sci. Technol. 41: 8178-8186.
34. Gyulkhandanyan AV, Feeney CJ, Pennefather PS. 2003. Modulation of mitochondrial membrane potential and reactive oxygen species production by copper in astrocytes. J. Neurochem. 87: 448-460.
35. Hafsi H, Hainaut P. 2011. Pharmacological rescue of p53 in cancer cells: the soloist meets the PRIMA donna. Cell Cycle 10: 873-878.
36. Ho E, Ames BN. 2002. Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFkappa B, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line. Proc. Natl. Acad. Sci. USA 99: 16770-16775.
37. Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT. 2004. Redox-active metals, oxidative stress, and Alzheimer's disease pathology. Ann. N. Y. Acad. Sci. 1012: 153-163.
38. Hussain SP, Raja K, Amstad PA, Sawyer M, Trudel LJ, Wogan GN, Hofseth LJ, Shields PG, Billiar TR, Trautwein C, Hohler T, Galle PR, Phillips DH, Markin R, Marrogi AJ, Harris CC. 2000. Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases. Proc. Natl. Acad. Sci. USA 97: 12770-12775.
39. Jomova K, Valko M. 2011. Advances in metal-induced oxidative stress and human disease. Toxicol. 283: 65-87.
40. Jomova K, Vondrakova D, Lawson M, Valko M. 2010. Metals, oxidative stress and neurodegenerative disorders. Mol. Cell. Biochem. 345: 91-104.
41. Kawakami M, Inagawa R, Hosokawa T, Saito T, Kurasaki M. 2008. Mechanism of apoptosis induced by copper in PC12 cells. Food Chem. Toxicol. 46: 2157-2164.
42. Khan HY, Zubair H Ullah MF, Ahmad A Hadi SM. 2011. Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism. Biometals 24: 1169-1178.
43. Kindermann B, Doring F, Pfaffl M, Daniel H. 2004. Identification of genes responsive to intracellular zinc depletion in the human colon adenocarcinoma cell line HT-29. J. Nutr. 134: 57-62.
44. 2+ release. J. Surg. Res. 153: 121-127.
45. Kohn KW. 1999. Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol. Biol. Cell 10: 2703-2734.
46. Kondoh M, Tasaki E, Araragi S, Takiguchi M, Higashimoto M, Watanabe Y, Sato M. 2002. Requirement of caspase and p38MAPK activation in zinc-induced apoptosis in human leukemia HL-60 cells. Eur. J. Biochem. 269: 6204-6211.
47. Kuo HW, Chen SF, Wu CC, Chen DR, Lee JH. 2002. Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol. Trace Elem. Res. 89: 1-11.
48. Lee JY, Cole TB, Palmiter RD, Suh SW, Koh JY. 2002. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc. Natl. Acad. Sci. USA 99: 7705-7710.
49. Levenson CW. 2005. Trace metal regulation of neuronal apoptosis: from genes to behaviour. Physiol. Behav. 86: 399-406.
50. Li PF, Dietz R, von Harsdorf R. 1999. p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J. 18: 6027-6036.
51. MacDonald RS. 2000. The role of zinc in growth and cell proliferation. J. Nutr. 130: 1500S-1508S.
52. Marcel V, Olivier M, Mollereau B, Hainaut P, Bourdon JC. 2011. First International p53 Isoforms Meeting: 'p53 isoforms through evolution: from identification to biological function. Cell Death Differ. 18: 563-564.
53. 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.
54. McCord JM. 2000. The evolution of free radicals and oxidative stress. Am. J. Med. 108: 652-659.
55. Meplan C, Richard MJ, Hainaut P. 2000. Metalloregulation of the tumor suppressor protein p53: zinc mediates therenaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene 19: 5227-5236.
56. Milacic V, Chen D, Giovagnini L, Diez A, Fregon D, Dou QP. 2008. Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity. Toxicol. Appl. Pharm.\ 231: 24-33.
57. Mori S, Ito G, Usami N, Yoshioka H, Ueda Y, Kodama Y, Takahashi M, Fong KM, Shimokata K, Sekido Y. 2004. p53 apoptotic pathway molecules are frequently and simultaneously altered in nonsmall cell lung carcinoma. Cancer 100: 1673-1682.
58. Narayanan VS, Fitch CA, Levenson CW. 2001. Tumor suppressor protein p53 mRNA and sub-cellular localization are altered by changes in cellular copper in human HepG2 cells. J. Nutr. 131: 1427-1432.
59. Noh SK, Koo SI. 2001. Feeding of a low-zinc diet lowers the tissue concentrations of alpha-tocopherol in adult rats. Biol. Trace Elem. Res. 81: 153-168.
60. Nyberg KA, Michelson RJ, Putnam CW, Weinert TA. 2002. Toward maintaining the genome: DNA damage and replication checkpoints. Annu. Rev. Genet. 36: 617-656.
61. Nzengue Y, Steiman R, Rachidi W, Favier A, Guiraud P. 2012. Oxidative stress induced by cadmium in the C6 cell line: role of copper and zinc. Biol. Trace Elem. Res. 146: 410-419.
62. Ostrakhovitch EA, Cherian MG. 2004. Differential regulation of signal transduction pathways in wild type and mutated p53 breast cancer epithelial cells by copper and zinc. Arch. Biochem. Biophys. 423: 351-361.
63. Ostrakhovitch EA, Cherian MG. 2005a. Inhibition of extracellular signal regulated kinase (ERK) leads to apoptosis inducing factor (AIF) mediated apoptosis in epithelial breast cancer cells: The lack of effect of ERK in p53 mediated copper induced apoptosis. J. Cell. Biochem. 95: 1120-1134.
64. Ostrakhovitch EA, Cherian MG 2005b. Role of p53 and reactive oxygen species in apoptotic response to copper and zinc in epithelial breast cancer cells. Apoptosis 10: 111-121.
65. Ostrakhovitch EA, Lordnejad MR, Schliess F, Sies H, Klotz LO. 2002. Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species. Arch. Biochem. Biophys. 397: 232-239.
66. Ostrakhovitch EA, Olsson PE, von Hofsten J, Cherian MG. 2007. P53 mediated regulation of metallothionein transcription in breast cancer cells. J. Cell. Biochem. 102: 1571-1583. DOI: 10.1002/jcb.21381.
67. Paris-Palacios S, Biangianti-Risbourg S. 2006. Hepatocyte nuclear structure and subcellular distribution of copper in zebrafish Brachydanio rerio and roach Rutilus rutilus (Teleostei Cyprinidae) exposed to copper sulphate. Aquat. Toxicol. 77: 306-313.
68. Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Poirier 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.
69. Peterson QP, Goode DR, West DC, Ramsey KN, Lee JJY, Hergenrother PJ. 2009. PAC-1 activates procaspase-3 in vitro through relief of zinc-mediated inhibition. J. Mol. Biol. 388: 144-158.
70. 2+. Toxicology 143: 263-273.
71. Pourahmad J, O'Brien PJ, Jokar F, Daraei B. 2003. Carcinogenic metal induced sites of reactive oxygen species formation in hepatocytes. Toxicol. in Vitro 17: 803-810.
72. Powell SR. 2000. The antioxidant properties of zinc. J. Nutr. 130: 1447S-1454S.
73. Powell CL, Swenberg JA, Rusyn I. 2005. Expression of base excision DNA repair genes as a biomarker of oxidative DNA damage. Cancer Lett. 229: 1-11.
74. Prasad AS. 2008. Clinical, immunological, anti-inflammatory and antioxidant roles of zinc. Exp. Gerontol. 43: 370-377.
75. Prasad AS. 2009. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr. Opin. Clin. Nutr. Metab. Care 12: 646-652.
76. Prasad AS, Bao B, Beck FWJ, Sarkar FH. 2001. Zinc activates NF-[kappa]B in HUT-78 cells. J. Lab. Clin. Med. 138: 250-256.
77. Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH. 2004. Antioxidant effect of zinc in humans. Free Radic. Biol. Med. 37: 1182-1190.
78. Prasad AS, Beck FWJ, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, Cardozo LJ. 2007. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am. J. Clin. Nutr. 85: 837-844.
79. 2+-induced apoptosis in cancer cells. Free Radic. Biol. Med. 32: 431-445.
80. Ra H, Kim HL, Lee HW, Kim YH. 2009. Essential role of p53 in TPEN-induced neuronal apoptosis. FEBS Lett. 583: 1516-1520.
81. Rostan EF, DeBuys HV, Madey DL, Pinnell SR. 2002. Evidence supporting zinc as an important antioxidant for skin. Int. J. Dermatol. 41: 606-611.
82. Rudolf E, Červinka M. 2008. External zinc stimulates proliferation of tumor Hep-2 cells by active modulation of key signaling pathways. J. Trace Elem. Med. Biol. 22: 149-161.
83. Sagripanti J, Goering PL, Lamanna A. 1991. Interaction of copper with DNA and antagonism by other metals. Toxicol. Appl. Pharm. 110: 477-485.
84. Samet JM, Graves LM, Quay J, Dailey LA, Devlin RB. 1998. Activation of MAPKs in human bronchial epithelial cells exposed to metals. Am. J. Physiol. 275: L551-L558.
85. Semczuk B, Pomykalski M. 1973. Serum copper level in patients with laryngeal carcinoma. Otolaryngol. Pol. 27: 17-23.
86. Simpson M, Xu Z. 2006. Increased abundance of labile intracellular zinc during cell proliferation was due to increased retention of extracellular zinc in 3T3 cells. J. Nutr. Biochem. 17: 541-547.
87. Stennicke HR, Salvesen GS. 1997. Biochemical characteristics of caspases-3, -6, -7, and -8. J. Biol. Chem. 272: 25719-25723.
88. Stohs SJ, Bagchi D. 1995. Oxidative mechanisms in the toxicity of metal ions. Free Radic. Biol. Med. 18: 321-336.
89. Su TT. 2006. Cellular responses to DNA damage: one signal, multiple choices. Annu. Rev. Genet. 40: 187-208.
90. Szuster-Ciesielska A, Stachura A, Slotwinska M, Kamińska T, Sniezko R, Paduch R, Abramczyk D, Filar J, Kandefer-Szerszeń M. 2000. The inhibitory effect of zinc on cadmium-induced cell apoptosis and reactive oxygen species (ROS) production in cell cultures. Toxicology 145: 159-171.
91. Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw W C. 1996. Cleavage of lamin 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.
92. Tang X, Shay NF. 2001. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J. Nutr. 131: 1414-1420.
93. Tassabehji NM, VanLandingham JW, Levenson CW. 2005. Copper alters the conformation and transcriptional activity of the tumor suppressor protein p53 in human Hep G2 cells. Exp. Biol. Med. 230: 699-708.
94. Thomas DJ, Caffrey TC. 1991. Lipopolysaccharide induces double-stranded DNA fragmentation in mouse thymus: protective effect of zinc pretreatment. Toxicology 68: 327-337.
95. Tkeshelashvili LK, McBride T, Spence K, Loeb LA. 1991. Mutation spectrum of copper-induced DNA damage. J. Biol. Chem. 266: 6401-6406.
96. Truong-Tran AQ, Ho LH, Chai F, Zalewski PD. 2000. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J. Nutr. 130: 1459S-1466S.
97. 2+ concentration in rabbit ventricular myocytes. Am. J. Physiol. 272: H2095-H2106.
98. VanLandingham JW, Fitch CA, Levenson CW. 2002. Zinc inhibits the nuclear translocation of the tumor suppressor protein p53 and protects cultured human neurons from copper-induced neurotoxicity. Neuromol. Med. 1: 171-182.
99. Vassort G, Turan B. 2010. Protective role of antioxidants in diabetes-induced cardiac dysfunction. Cardiovasc. Toxicol. 10: 73-86.
100. Verhaegh GW, Richard MJ, Hainaut P. 1997. Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper. Mol. Cell. Biol. 17: 5699-5706.
101. Veverka DV, Wilson C, Martinez MA, Wenger R, Tamosuinas A. 2009. Use of zinc supplements to reduce upper respiratory infections in United States Air Force Academy Cadets. Comp. Ther. Clin. Pract. 15: 91-95.
102. Wang X, Ou D, Yin J, Wu G, Wang J. 2009. Proteomic analysis reveals altered expression of proteins related to glutathione metabolism and apoptosis in the small intestine of zinc oxide-supplemented piglets. Amino Acids 37: 209-218.
103. Watjen W, Haase H, Biagioli M, Beyersmann D. 2002. Induction of apoptosis in mammalian cells by cadmium and zinc. Environ. Health Perspect. 110: 865-867.
104. Webster GA, Perkins ND. 1999. Transcriptional cross talk between NF-kappaB and p53. Mol. Cell. Biol. 19: 3485-3495.
105. White AR, Multhaup G, Maher F, Bellingham S, Camakaris J, Zheng H, Bush AI, Beyreuther K, Masters CL, Cappai R. 1999. The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures. J. Neurosci. 19: 9170-9179.
106. Wu W, Graves LM, Jaspers I, Devlin RB, Reed W. 1999. Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L924-L931.
107. 2+-induced cyclooxygenase-2 expression. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L883-L889.
108. Ye J, Wang S, Leonard SS, Sun Y, Butterworth L, Antonini J, Ding M, Rojanasakul Y, Vallyathan V, Castranova V, Shi X. 1999. Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis. J. Biol. Chem. 274: 34974-34980.
109. Zalewski PD, Forbes IJ, Giannakis C. 1991. Physiological role for zinc in prevention of apoptosis (gene-directed death). Biochem. Int. 24: 1093-1101.
110. Zhang X, Liang D, Guo B, Yang L, Wang L, Ma J. 2012. Zinc inhibits high glucose-induced apoptosis in peritoneal mesothelial cells. Biol. Trace Elem. Res. 150: 424-432.