Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec;397(1-2):187-94.
doi: 10.1007/s11010-014-2186-0. Epub 2014 Aug 20.

Epigenetic modifications and NF-κB pathway activity in Cu,Zn-SOD-deficient mice

Agnieszka Siomek  1 , Daniel Gackowski, Anna Szpila, Kamil Brzóska, Jolanta Guz, Barbara Sochanowicz, Marcin Kruszewski
Affiliations

Epigenetic modifications and NF-κB pathway activity in Cu,Zn-SOD-deficient mice

Agnieszka Siomek et al. Mol Cell Biochem. 2014 Dec.

Abstract

The aim of this study was to examine the possible impact of Cu,Zn-SOD deficiency on the level of epigenetic modifications in different mouse tissues, and the relationship between these modifications and the NF-κB transcription factor activity. Cu,Zn-SOD deficiency did not influence the level of 5mdC or 5hmdC in the analyzed tissues. Statistically significant organ-/tissue-specific differences between the levels of 5mdC and 5hmdC were demonstrated within each genotype. Also correlations between analyzed parameters pointed to wide tissue/genotype variety; we observed a positive correlation between 5mdC and NF-кB proteins, p50 and RelA, in the liver of wild mice, as well as an inverse correlation between 5mdC and p65 in the brain of Cu,Zn-SOD-deficient animals. Moreover, a positive correlation was revealed between 5mdC and 5hmdC in the liver and brain of knockout mice. As the highest levels of both 5mdC and 5hmdC were observed in the brains of analyzed animals regardless of their genotype, and lower, comparable to each other, levels of these modifications were shown in the kidney and liver, active demethylation process seems to be tissue-/organ-specific and does not necessarily rely solely on the redox/oxidation state of cells. According to the most likely scenario, various tissues may differ in terms of their metabolic rates, which has potential influence on cofactors, and consequently on the activity of TET enzymes or activation of TET-independent mechanisms.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Correlation between 5mdC and p50 protein in the liver of SOD1+/+ mice
Fig. 2
Fig. 2
Correlation between 5mdC and p65 protein in the liver of SOD1+/+ mice
Fig. 3
Fig. 3
Correlation between 5mdC and 5hmdC in the liver of SOD1−/− mice
Fig. 4
Fig. 4
Correlation between 5mdC and p65 in the brain of SOD1−/− mice
Fig. 5
Fig. 5
Correlation between 5mdC and 5 hmdC in the brain of SOD1−/− mice
See this image and copyright information in PMC

References

    1. Autry AE, Monteggia LM. Epigenetics in suicide and depression. Biol Psychiatry. 2009;66:812–813. doi: 10.1016/j.biopsych.2009.08.033. - DOI - PMC - PubMed
    1. Siedlecki P, Zielenkiewicz P. Mammalian DNA methyltransferases. Acta Biochim Pol. 2006;53:245–256. - PubMed
    1. Dahl C, Gronbaek K, Guldberg P. Advances in DNA methylation: 5-hydroxymethylcytosine revisited. Clin Chim Acta. 2011;412:831–836. doi: 10.1016/j.cca.2011.02.013. - DOI - PubMed
    1. Bhutani N, Burns DM, Blau HM. DNA demethylation dynamics. Cell. 2011;146:866–872. doi: 10.1016/j.cell.2011.08.042. - DOI - PMC - PubMed
    1. Penn NW, Suwalski R, O’Riley C, Bojanowski K, Yura R. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. 1972;126:781–790. - PMC - PubMed

Publication types

LinkOut - more resources