- Tytuł:
- Cu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity
- Autorzy:
-
Siomek, Agnieszka
Brzoska, Kamil
Sochanowicz, Barbara
Gackowski, Daniel
Rozalski, Rafal
Foksinski, Marek
Zarakowska, Ewelina
Szpila, Anna
Guz, Jolanta
Bartlomiejczyk, Teresa
Kalinowski, Bartlomiej
Kruszewski, Marcin
Olinski, Ryszard - Powiązania:
- https://bibliotekanauki.pl/articles/1042730.pdf
- Data publikacji:
- 2010
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
Cu,Zn-SOD deficiency
NF-κB pathway
oxidative stress - Opis:
- 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.
- Źródło:
-
Acta Biochimica Polonica; 2010, 57, 4; 577-583
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł