title: Epigenetic modifications and NF-κB pathway activity in Cu,Zn-SOD-deficient mice.
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.
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, ul. Karlowicza 24, 85-092, Bydgoszcz, Poland, asiomek@cm.umk.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Siomek
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
authors.forename: Anna
authors.initials: A
authors.lastname: Szpila
authors.forename: Kamil
authors.initials: K
authors.lastname: Brzóska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Guz
authors.forename: Barbara
authors.initials: B
authors.lastname: Sochanowicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D008099:Liver / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000172:deficiency*; D000072105:Superoxide Dismutase-1; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D052002:NF-kappa B p50 Subunit; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1