Journal
EPIGENETICS
Volume 8, Issue 7, Pages 730-738Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/epi.25012
Keywords
DNA methylation; glutathione; glutathione disulfide; homocysteine; oxidative stress; peripheral blood mononuclear cells; redox
Funding
- National Institutes of Health [RO1 CA133595, RO1 ES017875, P42 ES10349, P30 ES09089, 5-R25-CA 094061, T32 CA009529-24]
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Oxidative stress and DNA methylation are metabolically linked through the relationship between one-carbon metabolism and the transsulfuration pathway, but possible modulating effects of oxidative stress on DNA methylation have not been extensively studied in humans. Enzymes involved in DNA methylation, including DNA methyltransferases and histone deacetylases, may show altered activity under oxidized cellular conditions. Additionally, in vitro studies suggest that glutathione (GSH) depletion leads to global DNA hypomethylation, possibly through the depletion of S-adenosylmethionine (SAM). We tested the hypothesis that a more oxidized blood GSH redox status is associated with decreased global peripheral blood mononuclear cell (PBMC) DNA methylation in a sample of Bangladeshi adults. Global PBMC DNA methylation and whole blood GSH, glutathione disulfide (GSSG), and SAM concentrations were measured in 320 adults. DNA methylation was measured by using the [H-3]-methyl incorporation assay; values are inversely related to global DNA methylation. Whole blood GSH redox status (E-h) was calculated using the Nernst equation. We found that a more oxidized blood GSH E-h was associated with decreased global DNA methylation (B +/- SE, 271 +/- 103, p = 0.009). Blood SAM and blood GSH were associated with global DNA methylation, but these relationships did not achieve statistical significance. Our findings support the hypothesis that a more oxidized blood GSH redox status is associated with decreased global methylation of PBMC DNA. Furthermore, blood SAM does not appear to mediate this association. Future research should explore mechanisms through which cellular redox might influence global DNA methylation.
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