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. 2002 Oct;110(Suppl 5):807–811. doi: 10.1289/ehp.02110s5807

Signaling from toxic metals to NF-kappaB and beyond: not just a matter of reactive oxygen species.

Fei Chen 1, Xianglin Shi 1
PMCID: PMC1241250  PMID: 12426136

Abstract

The nuclear factor kappa B (NF-kappaB) family of transcription factors controls expression of a number of early response genes associated with inflammatory responses, cell growth, cell cycle progression, and neoplastic transformation. These genes include a multitude of cytokines, chemokines, adhesion molecules, immune receptors, stress proteins, apoptotic or anti-apoptotic regulators, and several oncogenes. Accumulating evidence indicates that a variety of toxic metals are able to affect the activation or activity of NF-kappaB, but the molecular mechanisms involved in this process remain largely unknown. The signaling pathways mediating cytokine- or microorganism-induced NF-kappaB activation have been well established recently. Whether the same signaling systems are involved in metal-induced NF-kappaB activation, however, is unclear. In the present review, we have attempted to evaluate and update the possible mechanisms of metal signals on the activation and function of NF-kappaB.

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Selected References

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  1. Alexander B. H., Checkoway H., Wechsler L., Heyer N. J., Muhm J. M., O'Keeffe T. P. Lung cancer in chromate-exposed aerospace workers. J Occup Environ Med. 1996 Dec;38(12):1253–1258. doi: 10.1097/00043764-199612000-00011. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. T., Staal F. J., Gitler C., Herzenberg L. A., Herzenberg L. A. Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11527–11531. doi: 10.1073/pnas.91.24.11527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrews G. K. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol. 2000 Jan 1;59(1):95–104. doi: 10.1016/s0006-2952(99)00301-9. [DOI] [PubMed] [Google Scholar]
  4. Baldwin A. S., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. doi: 10.1146/annurev.immunol.14.1.649. [DOI] [PubMed] [Google Scholar]
  5. Barbeau B., Bernier R., Dumais N., Briand G., Olivier M., Faure R., Posner B. I., Tremblay M. Activation of HIV-1 long terminal repeat transcription and virus replication via NF-kappaB-dependent and -independent pathways by potent phosphotyrosine phosphatase inhibitors, the peroxovanadium compounds. J Biol Chem. 1997 May 16;272(20):12968–12977. doi: 10.1074/jbc.272.20.12968. [DOI] [PubMed] [Google Scholar]
  6. Barceloux D. G. Chromium. J Toxicol Clin Toxicol. 1999;37(2):173–194. doi: 10.1081/clt-100102418. [DOI] [PubMed] [Google Scholar]
  7. Barchowsky A., Dudek E. J., Treadwell M. D., Wetterhahn K. E. Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med. 1996;21(6):783–790. doi: 10.1016/0891-5849(96)00174-8. [DOI] [PubMed] [Google Scholar]
  8. Beyersmann D. Interactions in metal carcinogenicity. Toxicol Lett. 1994 Jun;72(1-3):333–338. doi: 10.1016/0378-4274(94)90045-0. [DOI] [PubMed] [Google Scholar]
  9. Bowie A., O'Neill L. A. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol. 2000 Jan 1;59(1):13–23. doi: 10.1016/s0006-2952(99)00296-8. [DOI] [PubMed] [Google Scholar]
  10. Brennan P., O'Neill L. A. Effects of oxidants and antioxidants on nuclear factor kappa B activation in three different cell lines: evidence against a universal hypothesis involving oxygen radicals. Biochim Biophys Acta. 1995 Jan 25;1260(2):167–175. doi: 10.1016/0167-4781(94)00186-7. [DOI] [PubMed] [Google Scholar]
  11. Carter J. D., Ghio A. J., Samet J. M., Devlin R. B. Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol Appl Pharmacol. 1997 Oct;146(2):180–188. doi: 10.1006/taap.1997.8254. [DOI] [PubMed] [Google Scholar]
  12. Chaturvedi M. M., Mukhopadhyay A., Aggarwal B. B. Assay for redox-sensitive transcription factor. Methods Enzymol. 2000;319:585–602. doi: 10.1016/s0076-6879(00)19055-x. [DOI] [PubMed] [Google Scholar]
  13. Chen F., Castranova V., Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 2001 Aug;159(2):387–397. doi: 10.1016/s0002-9440(10)61708-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chen F., Demers L. M., Vallyathan V., Ding M., Lu Y., Castranova V., Shi X. Vanadate induction of NF-kappaB involves IkappaB kinase beta and SAPK/ERK kinase 1 in macrophages. J Biol Chem. 1999 Jul 16;274(29):20307–20312. doi: 10.1074/jbc.274.29.20307. [DOI] [PubMed] [Google Scholar]
  15. Chen F., Ding M., Castranova V., Shi X. Carcinogenic metals and NF-kappaB activation. Mol Cell Biochem. 2001 Jun;222(1-2):159–171. [PubMed] [Google Scholar]
  16. Chen F., Ding M., Lu Y., Leonard S. S., Vallyathan V., Castranova V., Shi X. Participation of MAP kinase p38 and IkappaB kinase in chromium (VI)-induced NF-kappaB and AP-1 activation. J Environ Pathol Toxicol Oncol. 2000;19(3):231–238. [PubMed] [Google Scholar]
  17. Chen F., Kuhn D. C., Sun S. C., Gaydos L. J., Demers L. M. Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages. Biochem Biophys Res Commun. 1995 Sep 25;214(3):839–846. doi: 10.1006/bbrc.1995.2363. [DOI] [PubMed] [Google Scholar]
  18. Chen F., Lu Y., Zhang Z., Vallyathan V., Ding M., Castranova V., Shi X. Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite. J Biol Chem. 2001 Jan 9;276(14):11414–11419. doi: 10.1074/jbc.M011682200. [DOI] [PubMed] [Google Scholar]
  19. Chen Fei, Bower Jacquelyn, Leonard Stephen S., Ding Min, Lu Yongju, Rojanasakul Yon, Kung Hsiang-fu, Vallyathan Val, Castranova Vince, Shi Xianglin. Protective roles of NF-kappa B for chromium(VI)-induced cytotoxicity is revealed by expression of Ikappa B kinase-beta mutant. J Biol Chem. 2001 Nov 28;277(5):3342–3349. doi: 10.1074/jbc.M101089200. [DOI] [PubMed] [Google Scholar]
  20. Christman J. W., Blackwell T. S., Juurlink B. H. Redox regulation of nuclear factor kappa B: therapeutic potential for attenuating inflammatory responses. Brain Pathol. 2000 Jan;10(1):153–162. doi: 10.1111/j.1750-3639.2000.tb00252.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Cortizo A. M., Bruzzone L., Molinuevo S., Etcheverry S. B. A possible role of oxidative stress in the vanadium-induced cytotoxicity in the MC3T3E1 osteoblast and UMR106 osteosarcoma cell lines. Toxicology. 2000 Jun 8;147(2):89–99. doi: 10.1016/s0300-483x(00)00181-5. [DOI] [PubMed] [Google Scholar]
  22. Flohé L., Brigelius-Flohé R., Saliou C., Traber M. G., Packer L. Redox regulation of NF-kappa B activation. Free Radic Biol Med. 1997;22(6):1115–1126. doi: 10.1016/s0891-5849(96)00501-1. [DOI] [PubMed] [Google Scholar]
  23. Ghosh S., May M. J., Kopp E. B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225–260. doi: 10.1146/annurev.immunol.16.1.225. [DOI] [PubMed] [Google Scholar]
  24. Hamilton J. W., Kaltreider R. C., Bajenova O. V., Ihnat M. A., McCaffrey J., Turpie B. W., Rowell E. E., Oh J., Nemeth M. J., Pesce C. A. Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect. 1998 Aug;106 (Suppl 4):1005–1015. doi: 10.1289/ehp.98106s41005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hanahan D., Weinberg R. A. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57–70. doi: 10.1016/s0092-8674(00)81683-9. [DOI] [PubMed] [Google Scholar]
  26. Haus B. M., Razavi H., Kuschner W. G. Occupational and environmental causes of bronchogenic carcinoma. Curr Opin Pulm Med. 2001 Jul;7(4):220–225. doi: 10.1097/00063198-200107000-00010. [DOI] [PubMed] [Google Scholar]
  27. Hayashi T., Ueno Y., Okamoto T. Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. J Biol Chem. 1993 May 25;268(15):11380–11388. [PubMed] [Google Scholar]
  28. Hehner S. P., Hofmann T. G., Ushmorov A., Dienz O., Wing-Lan Leung I., Lassam N., Scheidereit C., Dröge W., Schmitz M. L. Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IkappaB kinase complex. Mol Cell Biol. 2000 Apr;20(7):2556–2568. doi: 10.1128/mcb.20.7.2556-2568.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hu Y., Baud V., Oga T., Kim K. I., Yoshida K., Karin M. IKKalpha controls formation of the epidermis independently of NF-kappaB. Nature. 2001 Apr 5;410(6829):710–714. doi: 10.1038/35070605. [DOI] [PubMed] [Google Scholar]
  30. Imbert V., Peyron J. F., Farahi Far D., Mari B., Auberger P., Rossi B. Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide, an inhibitor of protein tyrosine phosphatases. Biochem J. 1994 Jan 1;297(Pt 1):163–173. doi: 10.1042/bj2970163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Israël A. The IKK complex: an integrator of all signals that activate NF-kappaB? Trends Cell Biol. 2000 Apr;10(4):129–133. doi: 10.1016/s0962-8924(00)01729-3. [DOI] [PubMed] [Google Scholar]
  32. Israël N., Gougerot-Pocidalo M. A., Aillet F., Virelizier J. L. Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines. J Immunol. 1992 Nov 15;149(10):3386–3393. [PubMed] [Google Scholar]
  33. Jaspers I., Samet J. M., Reed W. Arsenite exposure of cultured airway epithelial cells activates kappaB-dependent interleukin-8 gene expression in the absence of nuclear factor-kappaB nuclear translocation. J Biol Chem. 1999 Oct 22;274(43):31025–31033. doi: 10.1074/jbc.274.43.31025. [DOI] [PubMed] [Google Scholar]
  34. Jaspers I., Zhang W., Fraser A., Samet J. M., Reed W. Hydrogen peroxide has opposing effects on IKK activity and IkappaBalpha breakdown in airway epithelial cells. Am J Respir Cell Mol Biol. 2001 Jun;24(6):769–777. doi: 10.1165/ajrcmb.24.6.4344. [DOI] [PubMed] [Google Scholar]
  35. Kaltreider R. C., Pesce C. A., Ihnat M. A., Lariviere J. P., Hamilton J. W. Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Mol Carcinog. 1999 Jul;25(3):219–229. [PubMed] [Google Scholar]
  36. Kapahi P., Takahashi T., Natoli G., Adams S. R., Chen Y., Tsien R. Y., Karin M. Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem. 2000 Nov 17;275(46):36062–36066. doi: 10.1074/jbc.M007204200. [DOI] [PubMed] [Google Scholar]
  37. Karin M., Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000;18:621–663. doi: 10.1146/annurev.immunol.18.1.621. [DOI] [PubMed] [Google Scholar]
  38. Kishore Nandini, Huynh Q. Khai, Mathialagan Sumathy, Hall Troii, Rouw Sharon, Creely David, Lange Gary, Caroll James, Reitz Beverley, Donnelly Ann. IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. J Biol Chem. 2002 Feb 11;277(16):13840–13847. doi: 10.1074/jbc.M110474200. [DOI] [PubMed] [Google Scholar]
  39. Korn S. H., Wouters E. F., Vos N., Janssen-Heininger Y. M. Cytokine-induced activation of nuclear factor-kappa B is inhibited by hydrogen peroxide through oxidative inactivation of IkappaB kinase. J Biol Chem. 2001 Jul 30;276(38):35693–35700. doi: 10.1074/jbc.M104321200. [DOI] [PubMed] [Google Scholar]
  40. Krejsa C. M., Nadler S. G., Esselstyn J. M., Kavanagh T. J., Ledbetter J. A., Schieven G. L. Role of oxidative stress in the action of vanadium phosphotyrosine phosphatase inhibitors. Redox independent activation of NF-kappaB. J Biol Chem. 1997 Apr 25;272(17):11541–11549. doi: 10.1074/jbc.272.17.11541. [DOI] [PubMed] [Google Scholar]
  41. Lallena M. J., Diaz-Meco M. T., Bren G., Payá C. V., Moscat J. Activation of IkappaB kinase beta by protein kinase C isoforms. Mol Cell Biol. 1999 Mar;19(3):2180–2188. doi: 10.1128/mcb.19.3.2180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lee F. S., Peters R. T., Dang L. C., Maniatis T. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9319–9324. doi: 10.1073/pnas.95.16.9319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Li N., Karin M. Ionizing radiation and short wavelength UV activate NF-kappaB through two distinct mechanisms. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13012–13017. doi: 10.1073/pnas.95.22.13012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Li N., Karin M. Is NF-kappaB the sensor of oxidative stress? FASEB J. 1999 Jul;13(10):1137–1143. [PubMed] [Google Scholar]
  45. Marshall H. E., Merchant K., Stamler J. S. Nitrosation and oxidation in the regulation of gene expression. FASEB J. 2000 Oct;14(13):1889–1900. doi: 10.1096/fj.00.011rev. [DOI] [PubMed] [Google Scholar]
  46. Matthews J. R., Wakasugi N., Virelizier J. L., Yodoi J., Hay R. T. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res. 1992 Aug 11;20(15):3821–3830. doi: 10.1093/nar/20.15.3821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Mukhopadhyay A., Manna S. K., Aggarwal B. B. Pervanadate-induced nuclear factor-kappaB activation requires tyrosine phosphorylation and degradation of IkappaBalpha. Comparison with tumor necrosis factor-alpha. J Biol Chem. 2000 Mar 24;275(12):8549–8555. doi: 10.1074/jbc.275.12.8549. [DOI] [PubMed] [Google Scholar]
  48. Nakano H., Shindo M., Sakon S., Nishinaka S., Mihara M., Yagita H., Okumura K. Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3537–3542. doi: 10.1073/pnas.95.7.3537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Nelson N. Metal ion transporters and homeostasis. EMBO J. 1999 Aug 16;18(16):4361–4371. doi: 10.1093/emboj/18.16.4361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999 Mar 18;398(6724):252–256. doi: 10.1038/18465. [DOI] [PubMed] [Google Scholar]
  51. Nomura F., Kawai T., Nakanishi K., Akira S. NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation. Genes Cells. 2000 Mar;5(3):191–202. doi: 10.1046/j.1365-2443.2000.00315.x. [DOI] [PubMed] [Google Scholar]
  52. Peters R. T., Liao S. M., Maniatis T. IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Mol Cell. 2000 Mar;5(3):513–522. doi: 10.1016/s1097-2765(00)80445-1. [DOI] [PubMed] [Google Scholar]
  53. Pomerantz J. L., Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 1999 Dec 1;18(23):6694–6704. doi: 10.1093/emboj/18.23.6694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rangel M., Tamura A., Fukushima C., Sakurai H. In vitro study of the insulin-like action of vanadyl-pyrone and -pyridinone complexes with a VO(O4) coordination mode. J Biol Inorg Chem. 2001 Feb;6(2):128–132. doi: 10.1007/s007750000180. [DOI] [PubMed] [Google Scholar]
  55. Romashkova J. A., Makarov S. S. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999 Sep 2;401(6748):86–90. doi: 10.1038/43474. [DOI] [PubMed] [Google Scholar]
  56. Rossi A., Kapahi P., Natoli G., Takahashi T., Chen Y., Karin M., Santoro M. G. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature. 2000 Jan 6;403(6765):103–108. doi: 10.1038/47520. [DOI] [PubMed] [Google Scholar]
  57. Roussel R. R., Barchowsky A. Arsenic inhibits NF-kappaB-mediated gene transcription by blocking IkappaB kinase activity and IkappaBalpha phosphorylation and degradation. Arch Biochem Biophys. 2000 May 1;377(1):204–212. doi: 10.1006/abbi.2000.1770. [DOI] [PubMed] [Google Scholar]
  58. Ryan P. B., Huet N., MacIntosh D. L. Longitudinal investigation of exposure to arsenic, cadmium, and lead in drinking water. Environ Health Perspect. 2000 Aug;108(8):731–735. doi: 10.1289/ehp.00108731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Salnikow K., Su W., Blagosklonny M. V., Costa M. Carcinogenic metals induce hypoxia-inducible factor-stimulated transcription by reactive oxygen species-independent mechanism. Cancer Res. 2000 Jul 1;60(13):3375–3378. [PubMed] [Google Scholar]
  60. Schieven G. L., Kirihara J. M., Myers D. E., Ledbetter J. A., Uckun F. M. Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes. Blood. 1993 Aug 15;82(4):1212–1220. [PubMed] [Google Scholar]
  61. Senftleben U., Cao Y., Xiao G., Greten F. R., Krähn G., Bonizzi G., Chen Y., Hu Y., Fong A., Sun S. C. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001 Aug 24;293(5534):1495–1499. doi: 10.1126/science.1062677. [DOI] [PubMed] [Google Scholar]
  62. Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y., Kanamaru A., Akira S. IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Int Immunol. 1999 Aug;11(8):1357–1362. doi: 10.1093/intimm/11.8.1357. [DOI] [PubMed] [Google Scholar]
  63. Shumilla J. A., Broderick R. J., Wang Y., Barchowsky A. Chromium(VI) inhibits the transcriptional activity of nuclear factor-kappaB by decreasing the interaction of p65 with cAMP-responsive element-binding protein-binding protein. J Biol Chem. 1999 Dec 17;274(51):36207–36212. doi: 10.1074/jbc.274.51.36207. [DOI] [PubMed] [Google Scholar]
  64. Shumilla J. A., Wetterhahn K. E., Barchowsky A. Inhibition of NF-kappa B binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro: evidence of a thiol mechanism. Arch Biochem Biophys. 1998 Jan 15;349(2):356–362. doi: 10.1006/abbi.1997.0470. [DOI] [PubMed] [Google Scholar]
  65. Suzuki Y. J., Forman H. J., Sevanian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med. 1997;22(1-2):269–285. doi: 10.1016/s0891-5849(96)00275-4. [DOI] [PubMed] [Google Scholar]
  66. Suzuki Y. J., Packer L. Inhibition of NF-kappa B DNA binding activity by alpha-tocopheryl succinate. Biochem Mol Biol Int. 1993 Nov;31(4):693–700. [PubMed] [Google Scholar]
  67. Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K. NAK is an IkappaB kinase-activating kinase. Nature. 2000 Apr 13;404(6779):778–782. doi: 10.1038/35008109. [DOI] [PubMed] [Google Scholar]
  68. Toledano M. B., Leonard W. J. Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4328–4332. doi: 10.1073/pnas.88.10.4328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wang C., Deng L., Hong M., Akkaraju G. R., Inoue J., Chen Z. J. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001 Jul 19;412(6844):346–351. doi: 10.1038/35085597. [DOI] [PubMed] [Google Scholar]
  70. Ye J., Zhang X., Young H. A., Mao Y., Shi X. Chromium(VI)-induced nuclear factor-kappa B activation in intact cells via free radical reactions. Carcinogenesis. 1995 Oct;16(10):2401–2405. doi: 10.1093/carcin/16.10.2401. [DOI] [PubMed] [Google Scholar]
  71. Yin Z., Ivanov V. N., Habelhah H., Tew K., Ronai Z. Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases. Cancer Res. 2000 Aug 1;60(15):4053–4057. [PubMed] [Google Scholar]
  72. Zhang L., Rice A. B., Adler K., Sannes P., Martin L., Gladwell W., Koo J. S., Gray T. E., Bonner J. C. Vanadium stimulates human bronchial epithelial cells to produce heparin-binding epidermal growth factor-like growth factor: a mitogen for lung fibroblasts. Am J Respir Cell Mol Biol. 2001 Feb;24(2):123–131. doi: 10.1165/ajrcmb.24.2.4096. [DOI] [PubMed] [Google Scholar]

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