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Iron Supplementation Reverses Reduced Global Hydroxymethylcytosine Associated with Chronic Alcohol Consumption in Rats
Author(s) -
Choi Sang Woon,
Tammen Stephanie A,
Park Jung Eun,
Friso Simonetta,
Chung Jayong
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.912.6
Subject(s) - alcohol , 5 hydroxymethylcytosine , chemistry , dna demethylation , ferritin , dna methylation , transferrin , biochemistry , epigenetics , methylation , demethylation , transferrin receptor , medicine , cytosine , endocrinology , dna , biology , gene expression , gene
Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, aberrations of which can cause cancer development and progression. Iron is a cofactor of ten‐eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine, part of the demethylation process. We determined the influence of chronic alcohol consumption and iron supplementation on DNA methylation and hydroxymethylation using 24 male Sprague‐Dawley rats and Lieber‐DeCarli alcohol diets (36% calories from ethanol) along with iron supplementation (0.6% carbonyl iron). Hepatic non‐heme iron concentrations were measured by colorimetric assays. Protein levels of hepatic ferritin and transferrin receptor were determined by Western blotting. Methylcytosine, hydroxymethylcytosine and unmodified cytosine were measured using LC‐MS/MS method. Iron supplementation significantly increased hepatic non‐heme iron contents (p<0.05) but alcohol alone did not. On the other hand, both alcohol and iron significantly increased ferritin levels and decreased transferrin receptor levels (p<0.05). Alcohol reduced DNA hydroxymethylation (0.21 ± 0.04% vs 0.33 ± 0.04%, p = 0.01) compared to control, while iron supplementation to alcohol diet did not change DNA hydroxymethylation. There was no significant difference in methylcytosine levels, while unmodified cytosine levels were significantly increased in alcohol‐fed groups compared to control 95.61 ± 0.08% vs 95.26 ± 0.12%, p=0.03), suggesting that alcohol further increases the conversion from hydroxymethylcytosine to unmodified cytosine. Chronic alcohol consumption alters global DNA hydroxymethylation in the liver but iron supplementation reverses the epigenetic effect of alcohol. Support or Funding Information This work was supported in part by the Korean Food Research Institute (S.W.C.) and the Basic Science Research Program of the National Research Foundation (NRF‐2010‐0011226 to J.C.)