title: Alterations of phosphorylation state of connexin 43 during hypoxia and reoxygenation are associated with cardiac function.
abstract: Gap junctions formed by connexins mediate cell-cell communication by electrical and chemical coupling. Recently, it has been shown that alterations in the phosphorylation state of the connexins result in functional alteration of cell-cell communication through gap junctions. Therefore, we focused on the association of alterations of phosphorylation state of connexin 43 (Cx43) with cardiac function in vivo. Rat hearts were transferred to Langendorff apparatus and submitted to hypoxia and then reoxygenated. In the control heart, Cx43 was phosphorylated and located at the intercalated disk. When the hearts were subjected to hypoxia, Cx43 at gap junctions was dephosphorylated and changed its localization to the entire plasma membrane. The area of cardiomyocytes stained with anti-phosphorylated Cx43 antibody was decreased in a time-dependent manner. Immunoblot data supported the decrease of phosphorylated Cx43 during hypoxia. ZO-1 did not change its localization at the intercalated disk during the hypoxic period. We also found that the area occupied by dephosphorylated Cx43 was correlated with the decrease of percent of rate-pressure product. These data indicate that dephosphorylation and redistribution of Cx43 is an early sign of cardiac injury after hypoxia. Detection of dephosphorylated Cx43 may serve as a diagnostic tool for examining ischemic heart disease.
authors.affiliation: Department of Cardiovascular Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsushita
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.forename: Makino
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takao
authors.initials: T
authors.lastname: Okada
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Amano
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D010100:Oxygen / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017725:Ventricular Pressure; D062826:Zonula Occludens-1 Protein
chemical_list: D018031:Connexin 43; D008565:Membrane Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D001219:Aspartate Aminotransferases; D010100:Oxygen