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S‐adenosylmethionine Down Regulates Blood Alcohol Level
Author(s) -
BardagGorce Fawzia,
Oliva Joan,
Fong Stephanie,
Wong Wesley,
French Barbara A,
Li Jun,
French Samuel W
Publication year - 2010
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.24.1_supplement.236.7
Subject(s) - cyp2e1 , ethanol , alcohol dehydrogenase , aldehyde dehydrogenase , acetaldehyde , binge drinking , alcohol , chemistry , gene expression , ethanol metabolism , medicine , histone , endocrinology , enzyme , biochemistry , pharmacology , cytochrome p450 , gene , alcohol consumption
Alcohol consumption raises blood alcohol levels (BALs), and causes an increase in the enzymes that metabolize ethanol, primarily alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, s‐adenosylmethionine (SAMe) was observed to reduce acute BALs. The question is what is the mechanism involved in this reduction of BAL by SAMe feeding? To answer this question we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate these changes in acute binge drinking and chronic drinking. In the chronic model, rats were fed ethanol and SAMe for 1 month using the intragastric tube feeding model. In the acute models, rats were fed a bolus containing ethanol with or without SAMe and were sacrificed at 3 or 12 hours after the bolus. Western blot analyses showed that SAMe significantly induced ADH levels in the 3h liver samples. However, SAMe did not affect the changes in ADH levels for the 12h acute experiment or in the chronic experiment. Since SAMe is a methyl donor, it was suspected that the ADH gene expression change was due to a histone modification. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe in the acute experiments. These results correlate with the low BAL found in the acute experiment and support the concept that SAMe is a promising modulator of gene expression caused by high levels of ethanol. Supported by NIH/NIAAA 8116.