RGD Reference Report - Epigenetic modification of Sod2 in the development of diabetic retinopathy and in the metabolic memory: role of histone methylation. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Epigenetic modification of Sod2 in the development of diabetic retinopathy and in the metabolic memory: role of histone methylation.

Authors: Zhong, Q  Kowluru, RA 
Citation: Zhong Q and Kowluru RA, Invest Ophthalmol Vis Sci. 2013 Jan 14;54(1):244-50. doi: 10.1167/iovs.12-10854.
RGD ID: 9588312
Pubmed: PMID:23221071   (View Abstract at PubMed)
PMCID: PMC3590072   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.12-10854   (Journal Full-text)

PURPOSE: Mitochondrial superoxide levels are elevated in the retina in diabetes, and their scavenging enzyme, MnSOD, becomes subnormal. The objective of this study is to investigate the role of histone methylation of Sod2, the gene that encodes MnSOD, in the development of diabetic retinopathy and in the metabolic memory phenomenon associated with its continued progression after termination of hyperglycemia. METHODS: Effect of high glucose on monomethyl H3K4 (H3K4me1), dimethyl H3K4 (H3K4me2), and lysine-specific demethylase-1 (LSD1) was quantified at Sod2 by chromatin immunoprecipitation in isolated retinal endothelial cells. The role of histone methylation in the metabolic memory phenomenon was investigated in the retina of rats maintained in poor glycemic control (PC, approximately 12% glycated hemoglobin [GHb]) for 3 months followed by in good glycemic control (GC, approximately 6% GHb) for 3 months. RESULTS: Hyperglycemia reduced H3K4me1 and -me2, and increased the binding of LSD1 and Sp1 at Sod2. Regulation of LSD1 by LSD1-siRNA ameliorated glucose-induced decrease in H3K4 methylation at Sod2, and prevented decrease in Sod2 gene expression. In rats, re-institution of GC failed to reverse decrease in H3K4me1 and -me2 at Sod2, and LSD1 remained active with increased binding of LSD1 and Sp1 at Sod2. Retina from human donors with diabetic retinopathy also had decreased H3K4me2 and increased LSD1 at Sod2. CONCLUSIONS: Histone methylation of retinal Sod2 has an important role in the development of diabetic retinopathy and in the metabolic memory phenomenon associated with its continued progression. Targeting enzymes important for histone methylation may serve as a potential therapy to halt the development of diabetic retinopathy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein modification process  IEP 9588312histone H3-K4 demethylationRGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chromatin  IDA 9588312 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chromatin binding  IDA 9588312 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm1a  (lysine demethylase 1A)


Additional Information