Hyperthermia differently affects connexin43 expression and gap junction permeability in skeletal myoblasts and HeLa cells.

Hyperthermia differently affects connexin43 expression and gap junction permeability in skeletal myoblasts and HeLa cells.
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DOI:
10.1155/2014/748290
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发表时间:
2014
影响因子:
4.6
通讯作者:
Skeberdis VA
Skeberdis VA
中科院分区:
医学3区
文献类型:
--
作者:
Antanavičiūtė I;Mildažienė V;Stankevičius E;Herdegen T;Skeberdis VA

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应激激酶可被高温激活,并改变膜和细胞间通道的表达水平和性质。我们研究了c-Jun氨基末端激酶(JNK)在高血压诱导的兔骨骼肌成肌细胞(SkMs)和Cx43-EGFP转染的HeLa细胞中Cx43表达和Cx43间隙连接(GJs)通透性变化中的作用。在SkMs和HeLa细胞中,高温(42°C持续6小时)增强了JNK及其靶点(转录因子c-Jun)的活性。在SkMs中,高温导致总Cx43蛋白水平增加3.2倍,并增强了GJ细胞间通讯(GJIC)的功效。与此形成鲜明对比的是,高温降低了HeLa细胞中Cx43蛋白的总量、GJ斑块中Cx43通道的数量、细胞膜中半通道的密度和GJIC的效率。在SkMs和HeLa细胞中,这些变化可以被JNK抑制剂XG-102阻止。在HeLa细胞中,Cx43表达和GJIC在高温条件下的变化伴随着JNK依赖的肌动蛋白细胞骨架应力纤维的解体,而在SkMs中,肌动蛋白细胞骨架保持完整。这些发现提供了一个有吸引力的模型,以确定信号体内的监管球员,这决定了细胞依赖性的结果高热。
Stress kinases can be activated by hyperthermia and modify the expression level and properties of membranous and intercellular channels. We examined the role of c-Jun NH2-terminal kinase (JNK) in hyperthermia-induced changes of connexin43 (Cx43) expression and permeability of Cx43 gap junctions (GJs) in the rabbit skeletal myoblasts (SkMs) and Cx43-EGFP transfected HeLa cells. Hyperthermia (42°C for 6 h) enhanced the activity of JNK and its target, the transcription factor c-Jun, in both SkMs and HeLa cells. In SkMs, hyperthermia caused a 3.2-fold increase in the total Cx43 protein level and enhanced the efficacy of GJ intercellular communication (GJIC). In striking contrast, hyperthermia reduced the total amount of Cx43 protein, the number of Cx43 channels in GJ plaques, the density of hemichannels in the cell membranes, and the efficiency of GJIC in HeLa cells. Both in SkMs and HeLa cells, these changes could be prevented by XG-102, a JNK inhibitor. In HeLa cells, the changes in Cx43 expression and GJIC under hyperthermic conditions were accompanied by JNK-dependent disorganization of actin cytoskeleton stress fibers while in SkMs, the actin cytoskeleton remained intact. These findings provide an attractive model to identify the regulatory players within signalosomes, which determine the cell-dependent outcomes of hyperthermia.
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