Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
Channels (Austin). 2011 May-Jun;5(3):236-40. doi: 10.4161/chan.5.3.15834. Epub 2011 May 1.
The gap junction (GJ) protein connexin (Cx43) is important for organized action potential propagation between mammalian cardiomyocytes. Disruption of the highly ordered distribution of Cx43 GJs is characteristic of cardiac tissue after ischemic injury. We recently demonstrated that epicardial administration of a peptide mimetic of the Cx43 carboxyl-terminus reduced pathologic remodeling of Cx43 GJs and protected against induced arrhythmias following ventricular injury. Treatment of injuries with the carboxyl-terminal peptide was associated with an increase in phosphorylation at serine 368 of the Cx43 carboxyl-terminus. Here, we report that Cx43 peptide treatment of uninjured hearts does not prompt a similar increase in phosphorylation. Moreover, we show that peptide treatment of undisturbed cultured HeLa cells expressing a Cx43 construct also exhibit no changes in Cx43 phosphorylation at serine 368. However, in parallel with the results in vivo, a trend of increasing phosphorylation at serine 368 was observed in Cx43-expressing HeLa cells following scratch wounding of cultured monolayers. These results suggest that peptide-enhanced phosphorylation of the Cx43 carboxyl-terminus is dependent on injury-mediated cellular responses.
缝隙连接（GJ）蛋白连接蛋白（Cx43）对于哺乳动物心肌细胞之间有组织的动作电位传播很重要。Cx43 GJ 的高度有序分布的破坏是缺血性损伤后心脏组织的特征。我们最近证明，心脏外膜给予 Cx43 羧基末端模拟肽可减少 Cx43 GJ 的病理性重塑，并可预防心室损伤后诱导的心律失常。用羧基末端肽治疗损伤与 Cx43 羧基末端丝氨酸 368 的磷酸化增加有关。在这里，我们报告说，未受伤心脏的 Cx43 肽处理不会促使磷酸化增加类似。此外，我们还表明，用未受干扰的表达 Cx43 构建体的培养 HeLa 细胞处理肽也不会导致 Cx43 在丝氨酸 368 处的磷酸化发生变化。然而，与体内结果平行，在培养单层划痕损伤后，Cx43 表达的 HeLa 细胞中观察到丝氨酸 368 的磷酸化呈增加趋势。这些结果表明，肽增强的 Cx43 羧基末端磷酸化依赖于损伤介导的细胞反应。
