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High levels of glucose induce 'metabolic memory' in cardiomyocyte via epigenetic histone H3 lysine 9 methylation
- Source :
- Molecular Biology Reports. 39:8891-8898
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Diabetic patients continue to develop inflammation and cardiovascular complication even after achieving glycemic control, suggesting a "metabolic memory". Metabolic memory is a major challenge in the treatment of diabetic complication, and the mechanisms underlying metabolic memory are not clear. Recent studies suggest a link between chromatin histone methylation and metabolic memory. In this study, we tested whether histone 3 lysine-9 tri-methylation (H3K9me3), a key epigenetic chromatin marker, was involved in high glucose (HG)-induced inflammation and metabolic memory. Incubating cardiomyocyte cells in HG resulted in increased levels of inflammatory cytokine IL-6 mRNA when compared with myocytes incubated in normal culture media, whereas mannitol (osmotic control) has no effect. Chromatin immunoprecipitation (ChIP) assays showed that H3K9me3 levels were significantly decreased at the promoters of IL-6. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase, Suv39h1, were also reduced after HG treatment. HG-induced apoptosis, mitochondrial dysfunction and cytochrome-c release were reversible. However, the effects of HG on the expression of IL-6 and the levels of H3K9me3 were irreversible after the removal of HG from the culture. These results suggest that HG-induced sustained inflammatory phenotype and epigenetic histone modification, rather than HG-induced mitochondrial dysfunction and apoptosis, are main mechanisms responsible for metabolic memory. In conclusion, our data demonstrate that HG increases expression of inflammatory cytokine and decreases the levels of histone-3 methylation at the cytokine promoter, and suggest that modulating histone 3 methylation and inflammatory cytokine expression may be a useful strategy to prevent metabolic memory and cardiomyopathy in diabetic patients.
- Subjects :
- medicine.medical_specialty
Methyltransferase
Epigenetics in learning and memory
Biology
Methylation
Chromatin remodeling
Cell Line
Epigenesis, Genetic
Histones
Histone H3
Internal medicine
Histone methylation
Genetics
medicine
Humans
Myocytes, Cardiac
Epigenetics
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
Inflammation
Interleukin-6
Lysine
General Medicine
Molecular biology
Chromatin
Glucose
Endocrinology
Gene Expression Regulation
Cytokines
Inflammation Mediators
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 15734978 and 03014851
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Molecular Biology Reports
- Accession number :
- edsair.doi.dedup.....39e7277cbfea72f694fc05c661e55b99