Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses.
Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses.
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发表时间：
2003-11
期刊：
影响因子：
11.2
通讯作者：
E. Azzam;S. M. de Toledo;J. Little
中科院分区：
文献类型：
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作者：
E. Azzam;S. M. de Toledo;J. Little
为了更好地了解细胞对低剂量电离辐射的反应机制，用微阵列技术分析了低剂量α粒子照射下融合的人二倍体成纤维细胞的基因表达谱。这些数据得到了Northern和Western分析的支持，表明辐射诱导连接蛋白43的表达显著上调。这一现象在各种类型的受辐射细胞中都能观察到。这些发现与我们之前的观察一致，即连接蛋白43(Cx43)介导的缝隙连接细胞间通讯参与了暴露于α粒子的细胞培养中的旁观者反应，通过该反应，粒子轨迹只穿过很小一部分细胞核(E.I.Azzam等，Proc.娜塔莉。阿卡德。SCI。美国，98：473-478,2001)。照射后约4小时，细胞中Cx43蛋白水平的升高与照射后培养细胞中mRNA水平的升高有关。平均α粒子剂量低至0.16cGy时观察到Cx43的诱导，也观察到伽玛射线、叔丁基氢过氧化氢和高温对细胞的诱导作用。暴露在这些压力下也导致了Cx43的翻译后修饰；观察到该蛋白的磷酸化和过度磷酸化增加。在电离辐射暴露的细胞中，Cx43表达的上调与通过缝隙连接进行的功能通讯有关，这一点从照射细胞到非照射细胞的染料转移中得到了证明。相反，紫外线照射后的反应会有所不同，并与细胞类型有关。总体而言，这些数据表明，参与细胞间通讯的基因在调节细胞对各种压力的反应中发挥了关键作用。
To gain a greater understanding of the mechanisms underlying the cellular responses to low-dose ionizing radiation, gene expression profiles were examined by microarray analysis of cDNA from confluent human diploid fibroblast cultures exposed to very low fluences of alpha-particles. The data, supported by Northern and Western analyses, indicate that radiation induces a significant up-regulation of CONNEXIN43 expression. This phenomenon was observed in a variety of irradiated cell types. These findings are consistent with our previous observations that connexin43 (cx43)-mediated gap-junction intercellular communication is involved in the bystander response observed in cell cultures exposed to fluences of alpha-particles by which only a very small fraction of the cell nuclei is traversed by a particle track (E. I. Azzam et al., Proc. Natl. Acad. Sci. USA, 98: 473-478, 2001). Increased mRNA levels in cells from irradiated cultures correlated with increased cx43 protein levels by approximately 4 h after irradiation. The induction of cx43 was observed by mean alpha-particle doses as low as 0.16 cGy, and also in cells exposed to gamma-rays, t-butyl hydroperoxide, and hyperthermia. Exposure to these stresses also resulted in post-translational modification of cx43; increased phosphorylation and hyperphosphorylation of the protein was observed. Up-regulation of cx43 expression in ionizing radiation exposed cells correlated with functional communication through gap junctions, as evidenced by dye transfer from irradiated to nonirradiated cells. In contrast, the response after UV radiation varied and was cell type-dependent. Overall, these data suggest a critical role for genes involved in intercellular communication in mediating the cellular responses to a variety of stresses.