title: Alterations of connexin 43 in the diabetic rat heart.
abstract: In the streptozotocin-induced diabetic rat heart, a decrease in the conductivity and suppression of electrical cell-to-cell coupling has been observed. To clarify this mechanism, the present study was performed to investigate the gap junction connexin 43 (Cx43) using immunohistochemistry, immunoblot, electron-microscopic analyses. Enhanced activation of PKCepsilon, augmentation of PKCepsilon-mediated phosphorylation of Cx43, a decrease in the total amount of Cx43, a reduction in the number of immunoreactive particles for Cx43 at the intercalated disk and internalization, annular profiles of the gap junction were all recognized in the diabetic heart. Such a deterioration in the expression of Cx43 was alleviated by treatment with either lysosomal (leupeptin) or proteasomal inhibitor (ALLN). These results suggest that the PKCepsilon-mediated hyperphosphorylation of Cx43 makes Cx43 vulnerable to proteolytic degradation, while a decrease in the conductivity in the diabetic heart is also caused by a decrease in the number of gap junction channels due to an acceleration of the proteolytic degradation of Cx43. The remodeling of Cx43 induced by the activation of PKC may therefore contribute to the formation of the arrhythmogenic substrate.
authors.affiliation: Department of Physiology, Faculty of Medicine Fukuoka University, Fukuoka, Japan.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
authors.forename: Koichi
authors.initials: K
authors.lastname: Ogawa
authors.forename: Issei
authors.initials: I
authors.lastname: Imanaga
authors.forename: Narcis
authors.initials: N
authors.lastname: Tribulova
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
chemical_list: D018031:Connexin 43