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2010 | 57 | 4 | 577-583
Article title

Cu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity

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EN
Abstracts
EN
Earlier experimental studies have demonstrated that: i) Cu,Zn-superoxide dismutase deficiency leads to oxidative stress and carcinogenesis; ii) dysregulation of NF-κB pathway can mediate a wide variety of diseases, including cancer. Therefore, we decided, for the first time, to examine the level of oxidative DNA damage and the DNA binding activity of NF-κB proteins in SOD1 knockout, heterozygous and wild-type mice. Two kinds of biomarkers of oxidatively damaged DNA: urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively damaged DNA were analysed using HPLC-GC-MS and HPLC-EC. The DNA binding activity of p50 and p65 proteins in a nuclear extracts was assessed using NF-κB p50/p65 EZ-TFA transcription factor assay. These parameters were determined in the brain, liver, kidney and urine of SOD1 knockout, heterozygous and wild-type mice. The level of 8-oxodG in DNA was higher in the liver and kidney of knockout mice than in wild type. No differences were found in urinary excretion of 8-oxoGua and 8-oxodG between wild type and the SOD1-deficient animals. The activity of the p50 protein was higher in the kidneys, but surprisingly not in the livers of SOD1-deficient mice, whereas p65 activity did not show any variability. Our results indicate that in Cu,Zn-SOD-deficient animals the level of oxidative DNA damage and NF-κB1 activity are elevated in certain organs only, which may provide some explanation for organ-specific ROS-induced carcinogenesis.
Publisher

Year
Volume
57
Issue
4
Pages
577-583
Physical description
Dates
published
2010
received
2010-06-28
revised
2010-10-15
accepted
2010-11-03
(unknown)
2010-11-09
Contributors
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
author
  • Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland
  • Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
author
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
author
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
  • Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
  • Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland
  • Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland
References
  • Arai T, Kelly VP, Minowa O, Noda T, Nishimura S (2006) The study using wild-type and Ogg1 knockout mice exposed to potassium bromate shows no tumor induction despite an extensive accumulation of 8-hydroxyguanine in kidney DNA. Toxicology 221: 179-186.
  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.
  • Busuttil RA, Garcia AM, Cabrera C, Rodriguez A, Suh Y, Kim WH, Huang TT, Vijg J (2005) Organ-specific increase in mutation accumulation and apoptosis rate in Cu,Zn-superoxide dismutase-deficient mice. Cancer Res 65: 11271-11275.
  • Cooke MS, Olinski R, Evans MD (2006) Does measurement of oxidative damage to DNA have clinical significance? Clin Chim Acta 365: 30-49.
  • Dizdaroglu M (1994) Chemical determination of oxidative DNA damage by gas chromatography-mass spectrometry. Methods Enzymol 234: 3-16.
  • Djuric Z, Heilbrun LK, Lababidi S, Berzinkas E, Simon MS, Kosir MA (2001) Levels of 5-hydroxymethyl-2'-deoxyuridine in DNA from blood of women scheduled for breast biopsy. Cancer Epidemiol Biomarkers Prev 10: 147-149.
  • Douki T, Martini R, Ravanat JL, Turesky RJ, Cadet J (1997) Measurement of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 8-oxo-7,8-dihydroguanine in isolated DNA exposed to gamma radiation in aqueous solution. Carcinogenesis 18: 2385-2391.
  • Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson RL, Van RH, Epstein CJ, Huang TT (2005) CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24: 367-380.
  • Epe B (2002) Role of endogenous oxidative DNA damage in carcinogenesis: what can we learn from repair-deficient mice? Biol Chem 383: 467-475.
  • Fridovich I (1997) Superoxide anion radical (O2-.), superoxide dismutases, and related matters. J Biol Chem 272: 18515-18517.
  • Gackowski D, Rozalski R, Roszkowski K, Jawien A, Foksinski M, Olinski R (2001) 8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in human urine do not depend on diet. Free Radic Res 35: 825-832.
  • Gonzalez de Aguilar JL, Dupuis L, Oudart H, Loeffler JP (2005) The metabolic hypothesis in amyotrophic lateral sclerosis: insights from mutant Cu/Zn-superoxide dismutase mice. Biomed Pharmacother 59: 190-196.
  • Helbock HJ, Beckman KB, Shigenaga MK, Walter PB, Woodall AA, Yeo HC, Ames BN (1998) DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. Proc Natl Acad Sci USA 95: 288-293.
  • Ho YS, Gargano M, Cao J, Bronson RT, Heimler I, Hutz RJ (1998) Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem 273: 7765-7769.
  • Huang TT, Raineri I, Eggerding F, Epstein CJ (2002) Transgenic and mutant mice for oxygen free radical studies. Methods Enzymol 349: 191-213.
  • Johnson F, Giulivi C (2005) Superoxide dismutases and their impact upon human health. Mol Aspects Med 26: 340-352.
  • Kasai H (1997) Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 387: 147-163.
  • Kasprzak KS, Jaruga P, Zastawny TH, North SL, Riggs CW, Olinski R, Dizdaroglu M (1997) Oxidative DNA base damage and its repair in kidneys and livers of nickel(II)-treated male F344 rats. Carcinogenesis 18: 271-277.
  • Kruidenier L, van Meeteren ME, Kuiper I, Jaarsma D, Lamers CB, Zijlstra FJ, Verspaget HW (2003) Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice. Free Radic Biol Med 34: 753-765.
  • Luedde T, Beraza N, Kotsikoris V, van Loo G, Nenci A, De Vos R, Roskams T, Trautwein C, Pasparakis M (2007) Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11: 119-132.
  • Matzuk MM, Dionne L, Guo Q, Kumar TR, Lebovitz RM (1998) Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology 139: 4008-4011.
  • Naugler WE, Karin M (2008) NF-κB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 18: 19-26.
  • Olinski R, Gackowski D, Rozalski R, Foksinski M, Bialkowski K (2003) Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development? Mutat Res 531: 177-190.
  • Olinski R, Rozalski R, Gackowski D, Foksinski M, Siomek A, Cooke MS (2006) Urinary measurement of 8-oxodg, 8-oxoGua, and 5HMUra: a noninvasive assessment of oxidative damage to DNA. Antioxid Redox Signal 8: 1011-1019.
  • Oliver KM, Garvey JF, Ng CT, Veale DJ, Fearon U, Cummins EP, Taylor CT (2009) Hypoxia activates NF-κB-dependent gene expression through the canonical signaling pathway. Antioxid Redox Signal 11: 2057-2064.
  • Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18: 6853-6866.
  • Panzer U, Steinmetz OM, Turner JE, Meyer-Schwesinger C, von RC, Meyer TN, Zahner G, Gomez-Guerrero C, Schmid RM, Helmchen U, Moeckel GW, Wolf G, Stahl, RA, Thaiss F (2009) Resolution of renal inflammation: a new role for NF-κB1 (p50) in inflammatory kidney diseases. Am J Physiol Renal Physiol 297: F429-F439.
  • Ravanat JL, Guicherd P, Tuce Z, Cadet J (1999) Simultaneous determination of five oxidative DNA lesions in human urine. Chem Res Toxicol 12: 802-808.
  • Rojo AI, Salinas M, Martin D, Perona R, Cuadrado A (2004) Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-κB. J Neurosci 24: 7324-7334.
  • Sakurai T, He G, Matsuzawa A, Yu GY, Maeda S, Hardiman G, Karin M (2008) Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 14: 156-165.
  • Schoonbroodt S, Piette J (2000) Oxidative stress interference with the nuclear factor-kappa B activation pathways. Biochem Pharmacol 60: 1075-1083.
  • Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J 10: 2247-2258.
  • Sen R, Baltimore D (1986) Inducibility of kappa immunoglobulin enhancer-binding protein Nf-κB by a posttranslational mechanism. Cell 47: 921-928.
  • Sentman ML, Granstrom M, Jakobson H, Reaume A, Basu S, Marklund SL (2006) Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase. J Biol Chem 281: 6904-6909.
  • Shigenaga MK, Gimeno CJ, Ames BN (1989) Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci USA 86: 9697-9701.
  • Siomek A, Gackowski D, Rozalski R, Dziaman T, Szpila A, Guz J, Olinski R (2007) Higher leukocyte 8-oxo-7,8-dihydro-2'-deoxyguanosine and lower plasma ascorbate in aging humans? Antioxid Redox Signal 9: 143-150.
  • Sohal RS, Mockett RJ, Orr WC (2002) Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med 33: 575-586.
  • Wang T, Zhang X, Li JJ (2002) The role of NF-κB in the regulation of cell stress responses. Int Immunopharmacol 2: 1509-1520.
  • Weimann A, Riis B, Poulsen HE (2004) Oligonucleotides in human urine do not contain 8-oxo-7,8-dihydrodeoxyguanosine. Free Radic Biol Med 36: 1378-1382.
  • Yu Y, Wan Y, Huang C (2009) The biological functions of NF-κB1 (p50) and its potential as an anti-cancer target. Curr Cancer Drug Targets 9: 566-571.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv57p577kz
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