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

• Authors: Agnieszka Siomek , Kamil Brzoska , Barbara Sochanowicz , Daniel Gackowski , Rafal Rozalski , Marek Foksinski , Ewelina Zarakowska , Anna Szpila , Jolanta Guz , Teresa Bartlomiejczyk , Bartlomiej Kalinowski , Marcin Kruszewski , Ryszard Olinski
• Languages of publication: 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.

Keywords

EN

Cu,Zn-SOD deficiency; NF-κB pathway; oxidative stress

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2010
• Volume: 57
• Issue: 4
• Pages: 577-583

Dates

published

2010

received

2010-06-28

revised

2010-10-15

accepted

2010-11-03

(unknown)

2010-11-09

Contributors

author

Agnieszka Siomek

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Kamil Brzoska

• Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland

author

Barbara Sochanowicz

• Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland

author

Daniel Gackowski

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Rafal Rozalski

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Marek Foksinski

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Ewelina Zarakowska

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Anna Szpila

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Jolanta Guz

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Teresa Bartlomiejczyk

• Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland

author

Bartlomiej Kalinowski

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

author

Marcin Kruszewski

• Institute of Nuclear Chemistry and Technology, Centre of Radiobiology and Biological Dosimetry, Warszawa, Poland

author

Ryszard Olinski

• Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Department of Clinical Biochemistry, Bydgoszcz, Poland

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