Epigenetic Regulatory Effect of Exercise on Glutathione Peroxidase 1 Expression in the Skeletal Muscle of Severely Dyslipidemic Mice

Nguyen, Albert; Duquette, Natacha; Mamarbachi, Maya; Thorin, Éric

doi:10.1371/journal.pone.0151526

Cited by 20 publications

(16 citation statements)

References 73 publications

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“…The physiological role of the oxygen-responsive elements remains enigmatic, since gpx1 -/mice tolerated exposure to hyperbaric oxygen (85). Epigenetically, gpx1 transcription is downregulated by methylation of DNA methylation site (CpG) islets of the second exon (129).…”

Section: Gpx1mentioning

confidence: 99%

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Brigelius‐Flohé

Flohé

2020

Antioxidants & Redox Signaling

266

163

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Significance: The selenium-containing Glutathione peroxidases (GPxs)1-4 protect against oxidative challenge, inhibit inflammation and oxidant-induced regulated cell death. Recent Advances: GPx1 and GPx4 dampen phosphorylation cascades predominantly via prevention of inactivation of phosphatases by H 2 O 2 or lipid hydroperoxides. GPx2 regulates the balance between regeneration and apoptotic cell shedding in the intestine. It inhibits inflammation-induced carcinogenesis in the gut but promotes growth of established cancers. GPx3 deficiency facilitates platelet aggregation likely via disinhibition of thromboxane biosynthesis. It is also considered a tumor suppressor. GPx4 is expressed in three different forms. The cytosolic form proved to inhibit interleukin-1-driven nuclear factor jB activation and leukotriene biosynthesis. Moreover, it is a key regulator of ferroptosis, because it reduces hydroperoxy groups of complex lipids and silences lipoxygenases. By alternate substrate use, the nuclear form contributes to chromatin compaction. Mitochondrial GPx4 forms the mitochondrial sheath of spermatozoa and, thus, guarantees male fertility. Out of the less characterized GPxs, the cysteine-containing GPx7 and GPx8 are unique in contributing to oxidative protein folding in the endoplasmic reticulum by reacting with protein isomerase as an alternate substrate. A yeast 2-Cysteine glutathione peroxidase equipped with CP and CR was reported to sense H 2 O 2 for inducing an adaptive response. Critical Issues: Most of the findings compiled are derived from tissue culture and/or animal studies only. Their impact on human physiology is sometimes questionable. Future Directions: The expression of individual GPxs and GPx-dependent regulatory phenomena are to be further investigated, in particular in respect to human health. Antioxid. Redox Signal. 33, 498-516.

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Section: Gpx1mentioning

confidence: 99%

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Brigelius‐Flohé

Flohé

2020

Antioxidants & Redox Signaling

266

163

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“…To assess the impact of CpG5 methylation on ANGPTL2 expression, we used an in vitro methylation luciferase assay as previously described [ 54 – 56 ]. A 32 bp promoter sequence containing CpG5 was inserted into the pCpGfree-basic vector, upstream of a hEF-1α CpG-free promoter.…”

Section: Resultsmentioning

confidence: 99%

“…Constructions were done using the CpG free plasmid pCpGfree-promoter (Invivogen, San Diego, CA) as the backbone to study enhancer methylation. The ANGPTL2 CpG region was amplified using forward and reverse primers and subsequently inserted in the backbone using NsiI and BamHI restriction sites as previously described [ 54 , 55 ].…”

Section: Methodsmentioning

confidence: 99%

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Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients

et al. 2016

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DNA methylation is believed to regulate gene expression during adulthood in response to the constant changes in environment. The methylome is therefore proposed to be a biomarker of health through age. ANGPTL2 is a circulating pro-inflammatory protein that increases with age and prematurely in patients with coronary artery diseases; integrating the methylation pattern of the promoter may help differentiate age- vs. disease-related change in its expression. We believe that in a pro-inflammatory environment, ANGPTL2 is differentially methylated, regulating ANGPTL2 expression. To test this hypothesis we investigated the changes in promoter methylation of ANGPTL2 gene in leukocytes from patients suffering from post-acute coronary syndrome (ACS). DNA was extracted from circulating leukocytes of post-ACS patients with cardiovascular risk factors and from healthy young and age-matched controls. Methylation sites (CpGs) found in the ANGPTL2 gene were targeted for specific DNA methylation quantification. The functionality of ANGPTL2 methylation was assessed by an in vitro luciferase assay. In post-ACS patients, C-reactive protein and ANGPTL2 circulating levels increased significantly when compared to healthy controls. Decreased methylation of specific CpGs were found in the promoter of ANGPTL2 and allowed to discriminate age vs. disease associated methylation. In vitro DNA methylation of specific CpG lead to inhibition of ANGPTL2 promoter activity. Reduced leukocyte DNA methylation in the promoter region of ANGPTL2 is associated with the pro-inflammatory environment that characterizes patients with post-ACS differently from age-matched healthy controls. Methylation of different CpGs in ANGPTL2 gene may prove to be a reliable biomarker of coronary disease.

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“…38 In the face of environmental stresses, the expression of antioxidant enzymes including SOD2 and GPX1 were regulated by DNA methylation in the skeletal muscle of severely dyslipidemic mice. 39 In addition, DNA methylation analyses indicated CpG hypermethylation was detected in promoters of antioxidant genes including SOD1-3 and GPX catalyzed by DNTM1 in guinea pigs exposed to polymerized cell-free hemoglobin. 40 As the principal enzyme responsible for maintenance of CpG methylation, the expression of DNMT1 was signicantly elevated in replanted N. nucifera.…”

Section: Discussionmentioning

confidence: 99%