Dataset Information

Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

ABSTRACT:

Purpose

To elucidate the mechanism behind epigenetic alteration associated with dexamethasone (DEX) sodium phosphate treatment.

Methods

We performed enzyme-linked immunosorbent assay to quantify changes in global DNA methylation and hydroxymethylation, quantitative real-time PCR (qRT-PCR) of the DNA methylation- and hydroxymethylation-related gene, in vitro DNA methyltransferase (DNMT) enzymatic activity assays with purified DNMTs, and DNA hydroxymethylation pattern with super-resolution imaging.

Results

We identified global DNA hypomethylation and hyper-hydroxymethylation upon DEX treatment, associated with aberrant mRNA expression levels of DNMT and ten-eleven translocation (TET) proteins. Additionally, DEX exposure could directly hinder DNMT activities.

Conclusions

We showed that DEX-induced epigenetic alterations are linked to aberrant DNMT and TET expression, potentially through an essential role of DNMT.

SUBMITTER: Liu W

PROVIDER: S-EPMC8645185 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

Liu Wenjie W Mohan Sruthi Priya SP Nagaraj Nareshkumar Ragavachetty NR Sundar Jaganathan Shyam S Wen Yi Y Ramasubramanyan Sharada S Irudayaraj Joseph J

Molecular vision 20211120

<h4>Purpose</h4>To elucidate the mechanism behind epigenetic alteration associated with dexamethasone (DEX) sodium phosphate treatment.<h4>Methods</h4>We performed enzyme-linked immunosorbent assay to quantify changes in global DNA methylation and hydroxymethylation, quantitative real-time PCR (qRT-PCR) of the DNA methylation- and hydroxymethylation-related gene, in vitro DNA methyltransferase (DNMT) enzymatic activity assays with purified DNMTs, and DNA hydroxymethylation pattern with super-res ...[more]

PMID: 34924744

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Project description:BackgroundDexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia telangiectasia.MethodsThis is a post-hoc analysis of patients treated with EryDex for a minimum of 24 months in two prospective clinical trials. Outcomes include adverse events, growth, hemoglobin and serum iron, glucose levels, HbA1c, CD4+ lymphocytes, and bone mineral density.ResultsSixty-eight patients completed a minimum of 2 years of treatment with EryDex (mean treatment length 39 ± 11 months). Treatment-emergent adverse events (TEAE), reported in 67 (99%) out of 68 patients, were typically mild and did not cause discontinuation of treatment or death. Treatment-related TEAE were noted in 48 (71%) patients. Notable adverse events included transient pruritus reported in 23 (34%) patients and findings of low serum iron reported in 27 (40%) patients, while at baseline one fifth of patients had low serum iron. Anemia was reported in 9 (13%) patients. The mean hemoglobin level changed by -0.8 ± 1.0 g/dL after 6 months of therapy without subsequent decline. Longitudinal height and weight mean z-scores showed minimal change from baseline to month 24 for height (-0.06 ± 0.49), weight (-0.02 ± 0.71), and body mass index (0.03 ± 0.87). The mean bone mineral density (BMD) z-score showed a decline of 0.4 points over the 24 months of treatment. Values for glucose, HbA1c, cortisol, and CD4+ lymphocyte counts did not show clinically significant changes during prolonged treatment with EryDex.ConclusionThe most common treatment-related adverse events were transient infusion-related pruritus and iron deficiency. There was a decline in BMD which could not be distinguished from the natural course of disease. There were no adverse effects on height, weight and body mass index noted, as documented by stable z-scores throughout the 2 years of treatment. Adverse events typically observed with prolonged glucocorticoid use such as Cushingoid features, weight gain, hypertension, hirsutism, diabetes or stunted growth were rarely reported.Clinical trial registrationClinicalTrials.gov, identifiers: NCT02770807 and NCT03563053.

Dataset Information

Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

Purpose

Methods

Results

Conclusions

Publications

Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

Similar Datasets

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