Histone deacetylase inhibition reduces cardiac connexin43 expression and gap junction communication

Histone deacetylase inhibition reduces cardiac connexin43 expression and gap junction communication

Histone deacetylase inhibitors (HDACIs) are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDACIs on the functional expression of cardiac gap junctions (GJs) are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA) and vorinostat (VOR) on functional GJ expression in ventricular c...

Differential phosphorylation of the gap junction protein connexin43 in junctional communication-competent and -deficient cell lines

Connexin43 is a member of the highly homologous connexin family of gap junction proteins. We have studied how connexin monomers are assembled into functional gap junction plaques by examining the biosynthesis of connexin43 in cell types that differ greatly in their ability to form functional gap junctions. Using a combination of metabolic radiolabeling and immunoprecipitation, we have shown tha...

Inhibition of Histone Deacetylase Activity

Inhibition of Histone Deacetylase Suppresses

C-terminal truncation of connexin43 changes number, size, and localization of cardiac gap junction plaques.

Haplodeficient mice expressing carboxyl-terminally truncated Cx43 (K258stop/KO), instead of the wild-type Cx43 isoform, reach adulthood and reveal no abnormalities in heart morphology. Here, we have analyzed the expression of K258stop protein and the morphology of gap junctions in adult hearts of these mice. Coimmunofluorescence analysis revealed reduced juxtaposition of K258stop with other jun...