scholarly journals Epigenetic Modifications and Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Renu A. Kowluru ◽  
Julia M. Santos ◽  
Manish Mishra
Keyword(s):  
Diabetic Retinopathy ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Mitochondrial Superoxide ◽  
Micro Rnas ◽  
Genes Encoding ◽  
Lysine Demethylase ◽  
Metalloproteinase 9

Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

scholarly journals DNA Methyltransferase 3A Is Involved in the Sustained Effects of Chronic Stress on Synaptic Functions and Behaviors

2020 ◽  
Author(s):  
Jing Wei ◽  
Jia Cheng ◽  
Nicholas J Waddell ◽  
Zi-Jun Wang ◽  
Xiaodong Pang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Substantial Reduction ◽  
Dna Methyltransferases ◽  
Male Rats ◽  
Neural Pathways ◽  
Dnmt Inhibitors ◽  
Synaptic Functions

Abstract Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here, we found that male rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory, heightened aggression, and hyperlocomotion, were partially attenuated by Dnmt3a expression in PFC of stressed animals. Finally, we found that there were genome-wide DNA methylation changes and transcriptome alterations in PFC of stressed rats, both of which were enriched at several neural pathways, including glutamatergic synapse and microtubule-associated protein kinase signaling. These results have therefore recognized the potential role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive and emotional processes.

scholarly journals Two-dimensional electrophoresis protein profiles of HL-60 and CCRF-CEM cell lines treated with epigenetic modification drugs

2019 ◽  
pp. 10-23
Author(s):  
Aziee Sudin ◽  
Haiyuni Mohd Yassim ◽  
Shafini Mohamed Yusoff ◽  
Shaharum Shamsuddin ◽  
Ridhwan Abdul Wahab ◽  
...  
Keyword(s):  
Cell Lines ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Trichostatin A ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Epigenetic Modifications ◽  
Hematopoietic Stem ◽  
2D Gel

Leukemia is classified as a malignant disease of hematopoietic stem cells (HSCs) that fails in cell differentiation but preserve their self-renewal. It is caused by genetic alterations and epigenetic modifications resulting in the activation or inactivation of particular genes for transcription. Epigenetic causes changes in gene expression without any alteration in the DNA sequence. The most common epigenetic modifications are DNA methylation and histone acetylation. 5-Azacitidine (5-Aza) is a DNA methytransferase inhibitor (DNMTi) that inhibits DNA methyltransferase enzymes resulting in hypomethylation. Trichostatin A (TSA) is a histone deacetylase inhibitor which inhibits deacetylation of both histone and non-histone proteins resulting in chromatin relaxation. This present study focused on the alteration of proteome profile on 2D gel electrophoresis (2-DE) induced by 5-Aza and TSA in HL-60 and CCRF-CEM cell lines as in vitro model to represent acute promyelocytic leukemia (APL) and T-lymphoblastic leukemia (T-ALL), respectively. Total proteins of untreated and 5-Aza/TSA-treated HL-60 and CCRF-CEM cell lines were extracted using urea/thiourea buffer and stained with Coomassie Blue. Comparative analysis of untreated and 5-Aza/TSA-treated HL-60 and CCRF-CEM was performed by PDQuest software. Qualitative analysis identified 190-659 protein spots detected in untreated, 5-Aza and TSA-treated HL-60 and CCRF-CEM. Quantitative comparison analysis was analyzed by over 2-fold change in 5-Aza/TSA-treated cells compared to untreated. One and eight upregulated proteins were detected in 5-Aza and TSA-treated HL-60, respectively. While five and one upregulated proteins were detected in 5-Aza and TSA-treated CCRF-CEM, respectively. These preliminary results suggested that 5-Aza and TSA induced proteome profiles alterations due to their inhibition effects in HL-60 and CCRF-CEM cell lines.

scholarly journals Insights into novel emerging epigenetic drugs in myeloid malignancies

2019 ◽  
Vol 10 ◽  
pp. 204062071986608 ◽  
Author(s):  
Namrata S. Chandhok ◽  
Thomas Prebet
Keyword(s):  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
Epigenetic Modifications ◽  
Pharmacological Agents ◽  
Epigenetic Modifiers ◽  
The Us ◽  
Genes Encoding ◽  
Epigenetic Regulators ◽  
Heritable Phenotype

Epigenetics has been defined as ‘a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’ and several epigenetic regulators are recurrently mutated in hematological malignancies. Epigenetic modifications include changes such as DNA methylation, histone modifications and RNA associated gene silencing. Transcriptional regulation, chromosome stability, DNA replication and DNA repair are all controlled by these modifications. Mutations in genes encoding epigenetic modifiers are a frequent occurrence in hematologic malignancies and important in both the initiation and progression of cancer. Epigenetic modifications are also frequently reversible, allowing excellent opportunities for therapeutic intervention. The goal of epigenetic therapies is to reverse epigenetic dysregulation, restore the epigenetic balance, and revert malignant cells to a more normal condition. The role of epigenetic therapies thus far is most established in hematologic malignancies, with several agents already approved by the US Food and Drug Administration. In this review, we discuss pharmacological agents targeting epigenetic regulators.

scholarly journals Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

2021 ◽  
Vol 8 ◽  
Author(s):  
Rosaria Anna Fontanella ◽  
Lucia Scisciola ◽  
Maria Rosaria Rizzo ◽  
Surina Surina ◽  
Celestino Sardu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cells ◽  
Epigenetic Modification ◽  
Surrogate Marker ◽  
Left Ventricular ◽  
Epigenetic Modifications ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Plasma Mirna

In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.

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