The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M.; Görlach, Agnes

doi:10.1111/bph.13792

Cited by 189 publications

(142 citation statements)

References 238 publications

(336 reference statements)

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“…In conclusion, we have designed and validated a method to screen metabolites and chemicals for their effect on global methylation of newly synthesized DNA. Our results reveal a mechanism by which neutrophil-derived oxidants could inhibit maintenance methylation and thereby influence the course of disease (34)(35)(36).…”

Section: Discussionmentioning

confidence: 80%

Inhibition of DNA methylation in proliferating human lymphoma cells by immune cell oxidants

O’Connor

Das

Winterbourn

et al. 2020

Journal of Biological Chemistry

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Excessive generation of oxidants by immune cells results in acute tissue damage. One mechanism by which oxidant exposure could have long-term effects is modulation of epigenetic pathways. We hypothesized that methylation of newly synthesized DNA in proliferating cells can be altered by oxidants that target DNA methyltransferase activity or deplete its substrate, the methyl donor SAM. To this end, we investigated the effect of two oxidants produced by neutrophils, H2O2 and glycine chloramine, on maintenance DNA methylation in Jurkat T lymphoma cells. Using cell synchronization and MS-based analysis, we measured heavy deoxycytidine isotope incorporation into newly synthesized DNA and observed that a sublethal bolus of glycine chloramine, but not H2O2, significantly inhibited DNA methylation. Both oxidants inhibited DNA methyltransferase 1 activity, but only chloramine depleted SAM, suggesting that removal of substrate was the most effective means of inhibiting DNA methylation. These results indicate that immune cell–derived oxidants generated during inflammation have the potential to affect the epigenome of neighboring cells.

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Section: Discussionmentioning

confidence: 80%

Inhibition of DNA methylation in proliferating human lymphoma cells by immune cell oxidants

O’Connor

Das

Winterbourn

et al. 2020

Journal of Biological Chemistry

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“…ROS can directly convert 5-methylcytosin (5mC) to 5-hydroxymethylcytosine (5hmC) which blocks the activity of DNMT1 leading to an improper methylation inheritance during mitosis and global hypomethylation (144). Moreover ROS can oxidize guanosine to 8-oxo-20-deoxyguanosine (8-oxodG) thus inhibiting methylation of adjacent cytosine and further contributing to global hypomethylation of DNA (145,146). The formation of 8-oxodG in particular loci promotes the transcription of pro-inflammatory genes in response to TNF-α (147).…”

Section: Mitochondrial Ros and Epigenetic Changesmentioning

confidence: 99%

“…It contains the active methyl-donor group utilized by most methyltransferase enzymes. It has been demonstrated that ROS can reduce SAM availability, thus limiting the activity of DNA and histone methyltransferases (145). This is achieved either by inhibiting methionine adenosyl-transferase and thus SAM synthesis or by inhibiting methionine synthase and thus methionine regeneration (56).…”

Section: S-adenosylmethioninementioning

confidence: 99%

Epigenetic Control of Mitochondrial Function in the Vasculature

Mohammed

Ambrosini

Lüscher

et al. 2020

Front. Cardiovasc. Med.

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The molecular signatures of epigenetic regulation and chromatin architecture are emerging as pivotal regulators of mitochondrial function. Recent studies unveiled a complex intersection among environmental factors, epigenetic signals, and mitochondrial metabolism, ultimately leading to alterations of vascular phenotype and increased cardiovascular risk. Changing environmental conditions over the lifetime induce covalent and post-translational chemical modification of the chromatin template which sensitize the genome to establish new transcriptional programs and, hence, diverse functional states. On the other hand, metabolic alterations occurring in mitochondria affect the availability of substrates for chromatin-modifying enzymes, thus leading to maladaptive epigenetic signatures altering chromatin accessibility and gene transcription. Indeed, several components of the epigenetic machinery require intermediates of cellular metabolism (ATP, AcCoA, NADH, α-ketoglutarate) for enzymatic function. In the present review, we describe the emerging role of epigenetic modifications as fine tuners of gene transcription in mitochondrial dysfunction and vascular disease. Specifically, the following aspects are described in detail: (i) mitochondria and vascular function, (ii) mitochondrial ROS, (iii) epigenetic regulation of mitochondrial function; (iv) the role of mitochondrial metabolites as key effectors for chromatin-modifying enzymes; (v) epigenetic therapies. Understanding epigenetic routes may pave the way for new approaches to develop personalized therapies to prevent mitochondrial insufficiency and its complications.

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“…The ageing of the population will gradually increase the incidence of cardiovascular diseases, which seriously affects human health. In many physiological activities of the cardiovascular system, ROS are important signalling molecules that maintain the homeostasis of the internal environment of the cardiovascular system . A significant increase in ROS levels is closely related to the occurrence and development of cardiovascular diseases including heart failure, atherosclerosis, hypertension and ischaemic heart disease .…”

Section: Introductionmentioning

confidence: 99%

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

Hao

Zhang

et al. 2020

J Cellular Molecular Medi

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Oxidative stress injury is involved in many cardiovascular diseases, like hypertension and myocardial infarction. Ubiquitination is a ubiquitous protein post-translational modification that controls a wide range of biological functions and plays a crucial role in maintaining the homeostasis of cells in physiology and disease. Many studies have shown that oxidative stress damage is inextricably linked to ubiquitination. We demonstrate that Smurf2, an E3 ubiquitinated ligase, is involved in HUVEC apoptosis induced by oxidative stress to alleviate H 2 O 2 -induced reactive oxygen species (ROS) production and the apoptosis of human umbilical vein endothelial cells (HUVECs).At the same time, we found that Smurf2 can bind the poly(ADP-ribose) polymerase-1(PARP1), and the interaction is enhanced under the stimulation of oxidative stress.We further study and prove that Smurf2 can promote PARP1 ubiquitination and degradation. Collectively, we demonstrate Smurf2 degradation of overactivated PARP1 by ubiquitin-proteasome pathway to protect HUVEC and alleviate oxidative stress injury. K E Y W O R D Sapoptosis, Smurf2, ubiquitination | 4601 QIAN et Al.

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The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

Cited by 189 publications

References 238 publications

Inhibition of DNA methylation in proliferating human lymphoma cells by immune cell oxidants

Inhibition of DNA methylation in proliferating human lymphoma cells by immune cell oxidants

Epigenetic Control of Mitochondrial Function in the Vasculature

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

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