Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation
Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation
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DOI：
10.1152/ajpheart.00160.2009
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发表时间：
2010-03-01
影响因子：
4.8
通讯作者：
Tanabe, Teruhisa
中科院分区：
文献类型：
--
作者：
Amino, Mari;Yoshioka, Koichiro;Tanabe, Teruhisa
Amino M，Yoshioka K，Fujibayashi D，Hashida T，Furusawa Y，Zareba W，Ikari Y，Tanaka E，Mori H，Inokuchi S，Kodama I，Tanabe T。重离子照射兔心脏中连接蛋白43的长达一年的上调。 Am J Physiol Heart Circ Physiol 298：H1014-H1021，2010。首次发表于 2010 年 1 月 8 日； doi:10.1152/ajpheart.00160.2009.-我们实验室之前的一项研究表明，对兔心脏进行单次靶向重离子照射（THIR；15 Gy）可增加连接蛋白 43 (Cx43) 表达 2 周，并与传导改善、复极空间不均匀性减少以及心室脆弱性降低相关 心肌梗塞后的心律失常。本研究调查了 THIR (5-15 Gy) 对正常兔心脏 (n = 45) 中 Cx43 表达的时间和剂量依赖性影响。五只没有 THIR 的兔子被用作对照。免疫组织化学、蛋白质印迹和实时 PCR 发现，在 15 Gy 的单次 THIR 后 2 周至 1 年，心室肌中 Cx43 蛋白和 mRNA 显着上调。 THIR > 10 Gy 导致 THIR 后 2 周 Cx43 蛋白和 mRNA 显着剂量依赖性增加。左心室的前、侧、后游离壁、室间隔和右心室游离壁在 Cx43 上调方面也受到 THIR 的类似影响。放射诱导的免疫标记 Cx43 的增加不仅在闰盘区域而且在心室肌细胞的侧面也被观察到。免疫反应性Cx43蛋白的增加主要是在Triton X-100中不溶的膜部分，即肌膜中的Cx43。 THIR（15 Gy）后 1 年对兔子进行的体内检查显示心电图和超声心动图（左心室尺寸、收缩性和舒张功能）没有显着变化，表明没有明显的晚期放射损伤。单次应用 THIR 会导致心室中 Cx43 的上调和细胞分布改变，持续至少 1 年。这种对间隙连接的持久重塑作用可能为针对结构性心脏病中危及生命的室性心律失常的新疗法开辟道路。
Amino M, Yoshioka K, Fujibayashi D, Hashida T, Furusawa Y, Zareba W, Ikari Y, Tanaka E, Mori H, Inokuchi S, Kodama I, Tanabe T. Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation. Am J Physiol Heart Circ Physiol 298: H1014-H1021, 2010. First published January 8, 2010; doi:10.1152/ajpheart.00160.2009.-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 > 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.