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This study aims at investigating the epigenetic landscape of cardiomyocytes exposed to elevated glucose levels. High glucose (30 mM) for 72 hours determined some epigenetic changes in mouse HL-1 and rat differentiated H9C2 cardiomyocytes including upregulation of class I and III histone deacetylase protein levels and activity, inhibition of histone acetylase p300 activity, increase in histone H3 lysine 27 trimethylation, and reduction in H3 lysine 9 acetylation. Gene expression analysis focused on cardiotoxicity revealed that high glucose induced markers associated with tissue damage, fibrosis, and cardiac remodeling such as Nexilin (NEXN), versican, cyclic adenosine 5'-monophosphate-responsive element modulator (CREM), and adrenoceptor α2A (ADRA2). Notably, the transcription factor CREM was found to be important in the regulation of cardiotoxicity-associated genes as assessed by specific small interfering RNA and chromatin immunoprecipitation experiments. In CD1 mice, made hyperglycemic by streptozotoicin (STZ) injection, cardiac structural alterations were evident at 6 months after STZ treatment and were associated with a significant increase of H3 lysine 27 trimethylation and reduction of H3 lysine 9 acetylation. Consistently, NEXN, CREM, and ADRA2 expression was significantly induced at the RNA and protein levels. Confocal microscopy analysis of NEXN localization showed this protein irregularly distributed along the sarcomeres in the heart of hyperglycemic mice. This evidence suggested a structural alteration of cardiac Z-disk with potential consequences on contractility. In conclusion, high glucose may alter the epigenetic landscape of cardiac cells. Sildenafil, restoring guanosine 3', 5'-cyclic monophosphate levels, counteracted the increase of CREM and NEXN, providing a protective effect in the presence of hyperglycemia.
Pubmed ID: 28368536 RIS Download
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This unknown targets Synthetic peptide: CGG- DPEAAE, corresponding to amino acids 436-441 of Human Versican
View all literature mentionsThis monoclonal targets SIRT1
View all literature mentionsThis monoclonal targets Ryanodine Receptor
View all literature mentionsThis monoclonal targets Phospholamban
View all literature mentionsThis polyclonal targets Nexilin
View all literature mentionsThis polyclonal targets HDAC5
View all literature mentionsThis monoclonal targets HDAC4
View all literature mentionsThis polyclonal targets HDAC2 (H-54)
View all literature mentionsThis unknown targets Histone Deacetylase 1 (HDAC1)
View all literature mentionsThis polyclonal targets H3K27me3
View all literature mentionsThis polyclonal targets H3K9ac
View all literature mentionsThis polyclonal targets Histone H2A.X
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis monoclonal targets Fibrillarin
View all literature mentionsThis polyclonal targets Desmin
View all literature mentionsThis polyclonal targets Connexin 43 / GJA1 antibody
View all literature mentionsThis polyclonal targets CREM
View all literature mentionsThis polyclonal targets ADRA2A
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsCell line HL-1 is a Transformed cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line H9c2(2-1) is a Spontaneously immortalized cell line with a species of origin Rattus norvegicus (Rat)
View all literature mentionsCell line HL-1 is a Transformed cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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