Downregulation of connexin 43 gene expression in rat heart during inflammation. The role of tumour necrosis factor
Downregulation of connexin 43 gene expression in rat heart during inflammation. The role of tumour necrosis factor
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DOI：
10.1006/cyto.1998.0422
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发表时间：
1999-03-01
期刊：
影响因子：
3.8
通讯作者：
De Maio, A
中科院分区：
文献类型：
--
作者：
Fernandez-Cobo, M;Gingalewski, C;De Maio, A
间隙连接形成通道，介导相邻细胞之间的通讯。间隙连接功能和/或表达的改变被认为是导致心脏功能障碍的原因，例如在脓毒症患者中观察到的情况。在细菌脂多糖（LPS）诱导的炎症过程中，大鼠心脏中连接蛋白43 （Cx43）的亚基成分的表达被分析，Cx43 mRNA水平在注射LPS （1 mg/kg）后显著（约50%）和迅速（2小时）降低。为了研究炎症过程中Cx43表达降低的可能机制，我们克隆了该基因的启动子区域，在转染到大鼠成肌细胞系（H9c2）后，在转录起始位点224-134 bp范围内观察到Cx43启动子的基础活性，并且将转染的细胞与lps处理的大鼠血清孵育，发现Cx43启动子活性降低。与肿瘤坏死因子α孵育后，Cx43启动子活性也降低，这些结果表明Cx43在心脏中的表达可以通过循环细胞因子调节。这些观察结果可能对在脓毒症患者中观察到的心功能抑制有重要意义。(C) 1999学术出版社。
Gap junctions form channels that mediate the communication between adjacent cells. Alterations in gap junction function and/or expression are believed to contribute to cardiac dysfunction such as those observed in septic patients, The expression of connexin 43 (Cx43), the subunit component of the most abundant cardiac gap junction, was analysed in rat heart during inflammation induced by the administration of bacterial lipopolysaccharide (LPS), Cx43 mRNA levels were found to be dramatically (>50%) and rapidly (2 h) reduced in the heart after injection of LPS (I mg/kg). To investigate the possible mechanism of the decrease in Cx43 expression during inflammation, the promoter region of this gene was cloned, The basal Cx43 promoter activity was observed within 224-134 bp of the transcriptional initiation site after transfection into a rat myoblast cell-line (H9c2), The Cx43 promoter activity was found to be reduced by incubation of the transfected cells with serum obtained from LPS-treated rats,,Moreover, Cx43 promoter activity was also decreased upon incubation with tumour necrosis factor alpha, These results suggest that Cx43 expression in the heart can be modulated by circulating cytokines. These observations may hale important implications in the depression of heart function observed in septic patients. (C) 1999 Academic Press.