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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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Background: Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes. Methods: Twenty-four male Sprague-Dawley rats were fed either Lieber-DeCarli alcohol diet (36% calories from ethanol) or Lieber-DeCarli control diet along with or without iron supplementation (0.6% carbonyl iron) for 8 weeks. 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 in DNA were simultaneously measured by liquid chromatography/mass spectrometry method. Results: Iron supplementation significantly increased hepatic non-heme iron contents (P ＜ 0.05) but alcohol alone did not. However, both alcohol and iron significantly increased hepatic ferritin levels and decreased hepatic transferrin receptor levels (P ＜ 0.05). Alcohol reduced hepatic 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. Conclusions: Chronic alcohol consumption alters global DNA hydroxymethylation in the liver but iron supplementation reverses the epigenetic effect of alcohol.
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참고문헌 (30)
참고문헌 신청
Tammen SA / 2013 / Epigenetics: the link between nature and nurture / Mol Aspects Med 34:753~764
Tammen SA / 2014 / Aging and alcohol interact to alter hepatic DNA hydroxymethylation / Alcohol Clin Exp Res 38:2178~2185
Kudo Y / 2012 / Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation / Cancer Sci 103:670~676
Pfeifer GP / 2013 / 5-hydroxymethylcytosine and its potential roles in development and cancer / Epigenetics Chromatin 6:10
Chen ML / 2013 / Quantification of 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from hepatocellular carcinoma tissues by capillary hydrophilic-interaction liquid chromatography/quadrupole TOF mass spectrometry / Clin Chem 59:824~832
Tammen SA / 2014 / Aging and alcohol interact to alter hepatic DNA hydroxymethylation / Alcohol Clin Exp Res 38:2178~2185
Kudo Y / 2012 / Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation / Cancer Sci 103:670~676
Pfeifer GP / 2013 / 5-hydroxymethylcytosine and its potential roles in development and cancer / Epigenetics Chromatin 6:10
Chen ML / 2013 / Quantification of 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from hepatocellular carcinoma tissues by capillary hydrophilic-interaction liquid chromatography/quadrupole TOF mass spectrometry / Clin Chem 59:824~832
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