https://orcid.org/0000-0002-7828-6067
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ABSTRACT
The metabolism of DNA methylation is reported to be sensitive to oxidant molecules or oxidative stress. Hypothesis: early-life oxidative stress characterized by the redox potential of glutathione influences the DNA methylation level. The in vivo study aimed at the impact of modulating redox potential of glutathione on DNA methylation. Newborn guinea pigs received different nutritive modalities for 4 days: oral nutrition, parenteral nutrition including lipid emulsion Intralipid (PN-IL) or SMOFLipid (PN-SF), protected or not from ambient light. Livers were collected for biochemical determinations. Redox potential (p < 0.001) and DNA methylation (p < 0.01) were higher in PN-infused animals and even higher in PN-SF. Their positive correlation was significant (r2 = 0.51; p < 0.001). Methylation activity was higher in PN groups (p < 0.01). Protein levels of DNA methyltransferase (DNMT)-1 were lower in PN groups (p < 0.01) while those of both DNMT3a isoforms were increased (p < 0.01) and significantly correlated with redox potential (r2 > 0.42; p < 0.001). The ratio of SAM (substrate) to SAH (inhibitor) was positively correlated with the redox potential (r2 = 0.36; p < 0.001). In conclusion, early in life, the redox potential value strongly influences the DNA methylation metabolism, resulting in an increase of DNA methylation as a function of increased oxidative stress. These results support the notion that early-life oxidative stress can reprogram the metabolism epigenetically. This study emphasizes once again the importance of improving the quality of parenteral nutrition solutions administered early in life, especially to newborn infants.
Abbreviation of Title: Parenteral nutrition and DNA methylation
List of abbreviations
| 5-mC: 5-methylcytosine | = | |
| 5-MedCyd: 5’-methyl-2’ -deoxycytidine | = | |
| CpG dinucleotide: Cytosine-phosphate-Guanine dinucleotide | = | |
| DNA: Deoxyribonucleic acid | = | |
| DNMT: DNA methyltransferase | = | |
| GSH: Reduced glutathione | = | |
| GSSG: Oxidized glutathione | = | |
| IL: Intralipid emulsion | = | |
| LE: Light-exposed parenteral nutrition | = | |
| LP: Light-protected parenteral nutrition | = | |
| MAT: Methionine adenosyltransferase | = | |
| SAH: S-adenosyl homocysteine | = | |
| SAM: S-adenosyl methionine | = | |
| SF: SMOFlipid emulsion | = | |
| PN: Parenteral nutrition | = | |
| TET: Ten-eleven translocation protein | = |
Acknowledgments
We recognize the important participation of Mrs. Thérèse Rouleau who realized, among others, the catheterization of animals.
Disclosure statement
The authors declare no conflict of interest.
This work was supported by a grant from the Canadian Institutes of Health Research (PJT-148522).