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Review
. 2023 Mar 21;12(3):771.
doi: 10.3390/antiox12030771.

Nutriepigenomics in Environmental-Associated Oxidative Stress

Karla Rubio  1   2   3 , Estefani Y Hernández-Cruz  4   5 , Diana G Rogel-Ayala  2   3 , Pouya Sarvari  6 , Ciro Isidoro  7 , Guillermo Barreto  1   2   3 , José Pedraza-Chaverri  5
Affiliations
Review

Nutriepigenomics in Environmental-Associated Oxidative Stress

Karla Rubio et al. Antioxidants (Basel). .

Abstract

Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. In this review, we present an update on epigenetic mechanisms induced by environmental factors that lead to oxidative stress and potentially to pathogenesis and disease progression in humans. In addition, we introduce the microenvironment factors (physical contacts, nutrients, extracellular vesicle-mediated communication) that influence the epigenetic regulation of cellular responses. Understanding the mechanisms by which nutrients influence the epigenome, and thus global transcription, is crucial for future early diagnostic and therapeutic efforts in the field of environmental medicine.

Keywords: 2D culture; DNA methylation; antioxidants; extracellular vesicles; histone modifications; ncRNAs; nutrition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Role of oxidative stress in epigenetic modifications induced by environmental pollutants. ROS potentially interfere with the activity of DNMTs (1), their ability to methylate cytokines (2) or their union with the MBP complex (3). Guanine oxidation makes the methylated cytokine more susceptible to oxidation by TET enzymes (4). In addition, ROS deplete SAM by oxidizing MAT and MS (5) or by using homocysteine to regenerate GSH (6) causing DNA hypomethylation. However, ROS can also inhibit TETs (7). ONOO- nitrates histones (8), while reactive aldehydes modify histones by carbonylation (9). Glutathionylation is a relevant modification in histones due to oxidative stress (10). In addition, ROS either inhibit JmjC demethylases (11) or attenuate HMTs activity by decreased SAM (12). Additionally, ROS inhibit HDACs (13) and stimulate HATs (14). However, ROS could activate HDACs through an increase in NAD+ (15). Histones can be phosphorylated upon DNA damage (16). ROS causes deregulation of transcription factors (17), pre-miRNA synthesis by interaction with Fe3+ (18) and Dicer activity inhibition, which impairs miRNA maturation (19) and NRF2 levels (20). Created with biorender.com.
Figure 2
Figure 2
Cells in 2D culture undergo several epigenetic changes that allow them to adapt to their new environment. When cells or tissues are cultured (initial condition), they are affected by the change in environment, which, in turn, stimulates epigenetic modifications that allow the cell to adapt to the new conditions. These changes occur at different levels, histone modification, DNA methylation, the action of lncRNA in the nucleus, which are involved in the regulation of transcription and nuclear architecture, or its action in the nucleoplasm, where it influences RNA metabolism. Created with biorender.com.
Figure 3
Figure 3
Vitamins linking oxidative stress with epigenetics. The metabolism of dietary macronutrients produces ROS as side-products, which may contribute to inflammation-related diseases. However, intermediate metabolites and other dietary nutrients help the cell to face oxidative stress through epigenetic modulation of genes regulating the stress response. Overview of the metabolism of folic acid for the production of methyl donors (for DNA methylation). Created with biorender.com.
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