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

2.50
Hdl Handle:
http://hdl.handle.net/10146/190271
Title:
Cu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity.
Authors:
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
Abstract:
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.
Citation:
Acta Biochim. Pol. 2010, 57 (4):577-583
Journal:
Acta Biochimica Polonica
Issue Date:
2010
URI:
http://hdl.handle.net/10146/190271
PubMed ID:
21060899
Additional Links:
http://www.actabp.pl/pdf/4_2010/577.pdf
Type:
Article
Language:
en
ISSN:
1734-154X
Sponsors:
This work was supported by a grant from the Ministry of Science and Higher Education N301 2052 33 and in part by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).
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Full metadata record

DC FieldValue Language
dc.contributor.authorSiomek, Agnieszkaen
dc.contributor.authorBrzoska, Kamilen
dc.contributor.authorSochanowicz, Barbaraen
dc.contributor.authorGackowski, Danielen
dc.contributor.authorRozalski, Rafalen
dc.contributor.authorFoksinski, Mareken
dc.contributor.authorZarakowska, Ewelinaen
dc.contributor.authorSzpila, Annaen
dc.contributor.authorGuz, Jolantaen
dc.contributor.authorBartlomiejczyk, Teresaen
dc.contributor.authorKalinowski, Bartlomiejen
dc.contributor.authorKruszewski, Marcinen
dc.contributor.authorOlinski, Ryszarden
dc.date.accessioned2011-11-22T11:52:02Z-
dc.date.available2011-11-22T11:52:02Z-
dc.date.issued2010-
dc.identifier.citationActa Biochim. Pol. 2010, 57 (4):577-583en
dc.identifier.issn1734-154X-
dc.identifier.pmid21060899-
dc.identifier.urihttp://hdl.handle.net/10146/190271-
dc.description.abstractEarlier 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.en
dc.description.sponsorshipThis work was supported by a grant from the Ministry of Science and Higher Education N301 2052 33 and in part by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).en
dc.language.isoenen
dc.relation.urlhttp://www.actabp.pl/pdf/4_2010/577.pdfen
dc.subjectOxidative Stressen
dc.subjectDNA Damageen
dc.subjectCarcinogenesisen
dc.subjectSuperoxide Dismutaseen
dc.subjectNF-kappa Ben
dc.subjectMetabolismen
dc.subjectDeoxyguanosineen
dc.subjectGuanineen
dc.subjectAnimalsen
dc.subject.meshAnimals-
dc.subject.meshDNA Damage-
dc.subject.meshDeoxyguanosine-
dc.subject.meshFemale-
dc.subject.meshGuanine-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshNF-kappa B-
dc.subject.meshOxidative Stress-
dc.subject.meshSuperoxide Dismutase-
dc.titleCu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity.en
dc.typeArticleen
dc.identifier.journalActa Biochimica Polonicaen

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