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Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes
I Pérez-Torres1, M E Soto2, V Castrejón-Tellez3
1Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
Abstract:
Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.
Insights
Oxidative, reductive, and nitrosative stresses induce epigenetic changes impacting cardiometabolic health. These stress-induced modifications to DNA and proteins are reversible and potentially treatable.
Area of Science:
- Biochemistry
- Epigenetics
- Molecular Biology
Background:
- Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses involve interconnected reactions like carbonylation and nitration.
- These stresses arise from imbalances in antioxidant systems and nitric oxide (NO) metabolism.
Purpose of the Study:
- To explore the general characteristics of OS, RS, and NSS.
- To detail how these stresses induce DNA damage, histone modification, and alter epigenetic enzyme activities.
- To discuss the role of these stresses in cardiometabolic disorders and health heritability.
Main Methods:
- Review of biochemical reactions induced by OS, RS, and NSS.
- Analysis of posttranslational modifications on DNA, histones, and enzymes.
- Examination of the link between early-life stress exposure and adult cardiometabolic disease programming.
Main Results:
- OS, RS, and NSS induce DNA damage (e.g., 8-oxo-d guanosine) and modify histones.
- These stresses alter the activity of epigenetic enzymes (DNMTs, HMTs, HATs, HDACs) and DNA repair enzymes.
- Stress-induced epigenetic marks are established through reversible chemical modifications.
Conclusions:
- OS, RS, and NSS significantly impact cardiometabolic health through epigenetic reprogramming.
- Early-life environmental exposures mediated by these stresses can influence long-term health and heritability.
- The reversible nature of these epigenetic modifications offers potential therapeutic targets for cardiometabolic diseases.
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