title: Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation.
abstract: A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.
authors.affiliation: Dept. of Cardiology, Tokai Univ. School of Medicine, Isehara, Japan. mariam@is.icc.u-tokai.ac.jp
authors.forename: Mari
authors.initials: M
authors.lastname: Amino
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujibayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hashida
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikari
authors.forename: Etsuro
authors.initials: E
authors.lastname: Tanaka
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Sadaki
authors.initials: S
authors.lastname: Inokuchi
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D002244:Carbon; D018031:Connexin 43 / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D006321:Heart / Q000528:radiation effects*; D006352:Heart Ventricles / Q000378:metabolism / Q000528:radiation effects; D020450:Heavy Ions; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011829:Radiation Dosage; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; D012333:RNA, Messenger; D002244:Carbon