scholarly journals Mitochondria DNA Replication and DNA Methylation in the Metabolic Memory Associated with Continued Progression of Diabetic Retinopathy

2012 ◽  
Vol 53 (8) ◽  
pp. 4881 ◽  
Author(s):  
Shikha Tewari ◽  
Qing Zhong ◽  
Julia M Santos ◽  
Renu A Kowluru
Keyword(s):  
Dna Methylation ◽  
Diabetic Retinopathy ◽  
Dna Replication ◽  
Metabolic Memory ◽  
Mitochondria Dna

scholarly journals Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Alexey A. Leontovich ◽  
Robert V. Intine ◽  
Michael P. Sarras
Keyword(s):  
Dna Methylation ◽  
Cell Proliferation ◽  
Dna Replication ◽  
Bioinformatics Analysis ◽  
Repair Process ◽  
Metabolic Memory ◽  
Transcription Start ◽  
Diabetic Model ◽  
Repair Genes

Metabolic memory (MM) is defined as the persistence of diabetic (DM) complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of theDNA replication/DNA metabolism processgroup (with upregulation of theapex1, mcm2, mcm4, orc3,lig1, anddnmt1 genes) were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6–13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of theDNA replication/repair processgroup best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.

scholarly journals Diabetic Retinopathy: Mitochondria Caught in a Muddle of Homocysteine

2020 ◽  
Vol 9 (9) ◽  
pp. 3019
Author(s):  
Renu A. Kowluru
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Diabetic Retinopathy ◽  
Diabetic Patients ◽  
Vicious Cycle ◽  
Protein Amino Acid ◽  
Mtdna Damage ◽  
Mitochondrial Homeostasis ◽  
Systemic Factors ◽  
Adenosyl Methionine

Diabetic retinopathy is one of the most feared complications of diabetes. In addition to the severity of hyperglycemia, systemic factors also play an important role in its development. Another risk factor in the development of diabetic retinopathy is elevated levels of homocysteine, a non-protein amino acid, and hyperglycemia and homocysteine are shown to produce synergistic detrimental effects on the vasculature. Hyperhomocysteinemia is associated with increased oxidative stress, and in the pathogenesis of diabetic retinopathy, oxidative stress-mitochondrial dysfunction precedes the development of histopathology characteristic of diabetic retinopathy. Furthermore, homocysteine biosynthesis from methionine forms S-adenosyl methionine (SAM), and SAM is a co-substrate of DNA methylation. In diabetes, DNA methylation machinery is activated, and mitochondrial DNA (mtDNA) and several genes associated with mitochondrial homeostasis undergo epigenetic modifications. Consequently, high homocysteine, by further affecting methylation of mtDNA and that of genes associated with mtDNA damage and biogenesis, does not give any break to the already damaged mitochondria, and the vicious cycle of free radicals continues. Thus, supplementation of sensible glycemic control with therapies targeting hyperhomocysteinemia could be valuable for diabetic patients to prevent/slow down the development of this sight-threatening disease.

Delayed DNA methylation is an integral feature of DNA replication in mammalian cells

1986 ◽  
Vol 166 (1) ◽  
pp. 103-112 ◽  
Author(s):  
D.M. Woodcock ◽  
D.L. Simmons ◽  
P.J. Crowther ◽  
I.A. Cooper ◽  
K.J. Trainor ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Replication ◽  
Mammalian Cells ◽  
Integral Feature
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