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

摘要

据报道，DNA甲基化的代谢对氧化剂分子或氧化应激敏感。假设：以谷胱甘肽的氧化还原电位为特征的生命早期氧化应激会影响DNA甲基化水平。该体内研究旨在对DNA甲基化调控的谷胱甘肽氧化还原电位的影响。新生豚鼠在4天内接受了不同的营养方式：口服营养，肠胃外营养（包括脂质乳剂，脂质体内，（PN-IL）或SMOFLipid（PN-SF）），是否受到外界光照的保护。收集肝脏用于生化测定。PN灌注动物的氧化还原电势（p <0.001）和DNA甲基化（p <0.01）更高，而PN-SF更高。他们的正相关性显着（r ² = 0.51; p <0.001）。PN组的甲基化活性较高（p <0.01）。PN组的DNA甲基转移酶（DNMT）-1蛋白质水平较低（p <0.01），而DNMT3a两种亚型的蛋白质水平均升高（p <0.01），并且与氧化还原电位显着相关（r ²  > 0.42; p <0.001）。SAM（底物）与SAH（抑制剂）的比例与氧化还原电位呈正相关（r ² = 0.36; p <0.001）。总之，在生命的早期，氧化还原电位值会强烈影响DNA甲基化代谢，导致DNA甲基化的增加是氧化应激增加的函数。这些结果支持了早期氧化应激可以表观遗传地重新编程代谢的观点。这项研究再次强调了改善生命早期尤其是对婴儿的肠胃外营养液质量的重要性。

标题的缩写：肠胃外营养与DNA甲基化