RGD Reference Report - Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. - Rat Genome Database

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Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy.

Authors: Zhong, Q  Kowluru, RA 
Citation: Zhong Q and Kowluru RA, Diabetes. 2011 Apr;60(4):1304-13. doi: 10.2337/db10-0133. Epub 2011 Feb 25.
RGD ID: 9586742
Pubmed: PMID:21357467   (View Abstract at PubMed)
PMCID: PMC3064104   (View Article at PubMed Central)
DOI: DOI:10.2337/db10-0133   (Journal Full-text)

OBJECTIVE: To investigate the role of epigenetic regulation of the manganese superoxide dismutase gene (sod2) in the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression after hyperglycemia is terminated. RESEARCH DESIGN AND METHODS: Streptozotocin-induced diabetic rats were maintained in poor glycemic control (PC, GHb approximately 12%) or in good glycemic control (GC, GHb ~7.0%) for 4 months, or were allowed to maintain PC for 2 months, followed by GC for 2 additional months (PC-Rev). For experimental galactosemia, a group of normal rats were fed a 30% galactose diet for 4 months or for 2 months, followed by a normal diet for 2 additional months. Trimethyl histone H4 lysine 20 (H4K20me3), acetyl histone H3 lysine 9 (H3K9), and nuclear transcriptional factor NF-kappaB p65 and p50 at the retinal sod2 promoter and enhancer were examined by chromatin immunoprecipitation. RESULTS: Hyperglycemia (diabetes or galactosemia) increased H4K20me3, acetyl H3K9, and NF-kappaB p65 at the promoter and enhancer of retinal sod2, upregulated protein and gene expression of SUV420h2, and increased the interactions of acetyl H3K9 and NF-kappaB p65 to H4K20me3. Reversal of hyperglycemia failed to prevent increases in H4K20me3, acetyl H3K9, and NF-kappaB p65 at sod2, and sod2 and SUV420h2 continued to be abnormal. Silencing SUV420h2 by its small interfering RNA in retinal endothelial cells prevented a glucose-induced increase in H4K20me3 at the sod2 enhancer and a decrease in sod2 transcripts. CONCLUSIONS: Increased H4K20me3 at sod2 contributes to its downregulation and is important in the development of diabetic retinopathy and in the metabolic memory phenomenon. Targeting epigenetic changes may serve as potential therapeutic targets to retard the development and progression of diabetic retinopathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOKmt5c (Rattus norvegicus)9586742; 9586742mRNA:increased expression:retinaRGD 
Experimental Diabetes Mellitus  IEP 9586742mRNA:increased expression:retinaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kmt5c  (lysine methyltransferase 5C)

Genes (Mus musculus)
Kmt5c  (lysine methyltransferase 5C)

Genes (Homo sapiens)
KMT5C  (lysine methyltransferase 5C)


Additional Information