title: Internalization and dephosphorylation of connexin43 in hypertrophied right ventricles of rats with pulmonary hypertension.
abstract: BACKGROUND
  Altered expression and distribution of gap junctions might provide substrates for abnormal conduction and arrhythmogenesis in the heart, but little is known about the regulation of gap junctions under pathological conditions. The organization and phosphorylation state of connexin43 (Cx43) in ventricular hypertrophy will be investigated.
  
  
  RESULTS
  Right ventricular (RV) hypertrophy was induced in rats by treatment with monocrotaline. Subcellular Cx43 distribution was assessed by immunoconfocal and electron microscopy. Immunolabeling of Cx43 was confined to the intercalated disks in the normal ventricular myocytes of control rats, but hypertrophied RV cells from monocrotaline-treated rats showed dispersion of Cx43 immunolabeling over the cell surface and in the cytoplasm; cytoplasmic Cx43 was increased by approximately 7-fold (n=15). The Cx43 internalization was confirmed by the double staining of monocrotaline-treated RV tissues for Cx43/wheat germ agglutinin (WGA) and Cx43/zonula occludens protein-1 (ZO-1). Electron microscopy of hypertrophied RVs showed an increase in annular gap junctions immunolabeled with Cx43. Immunoblotting revealed a significant increase in non-phosphorylated Cx43 in hypertrophied RVs (by approximately 5-fold, n=8) without changes in the total amount of Cx43. The accumulation of non-phosphorylated Cx43 in hypertrophied RVs was also recognized by immunoconfocal-microscopy with an isoform-specific antibody.
  
  
  CONCLUSIONS
  Ventricular hypertrophy is associated with the dephosphorylation of Cx43 and its translocation from the intercalated disks to intracellular pools, suggesting accelerated gap junction degradation.
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Sasano
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takagishi
authors.forename: Mahmud
authors.initials: M
authors.lastname: Uzzaman
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.forename: Atsuya
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000032:analysis* / Q000378:metabolism*; D004195:Disease Models, Animal; D004705:Endocytosis; D017629:Gap Junctions / Q000737:chemistry / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000150:complications*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D018031:Connexin 43