Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain.
PLoS One. 2012;7(11):e48957. doi: 10.1371/journal.pone.0048957. Epub 2012 Nov 12.
The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function.
A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively).
This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.
本研究旨在分析心力衰竭（HF）对核孔复合体（NPC）中几种蛋白的影响，并探讨其与人类心室功能的关系。
采用 Western blot 法对 88 例因缺血（ICM，n=52）和扩张型（DCM，n=36）心肌病行心脏移植的患者及对照组供体（CNT，n=9）的心脏组织样本进行分析。通过荧光和免疫细胞化学分析核孔蛋白的亚细胞分布。当我们根据病因比较蛋白水平时，ICM 组的 NDC1（65%，p<0.0001）、Nup160（88%，p<0.0001）和 Nup153（137%，p=0.004）水平显著高于 CNT 组。此外，DCM 组的 NDC1（41%，p<0.0001）、Nup160（65%，p<0.0001）、Nup153（155%，p=0.006）和 Nup93（88%，p<0.0001）水平与 CNT 组相比差异均有统计学意义。然而，Nup155 和转位启动子区（TPR）在任何病因中其水平均无显著差异。关于这些蛋白在细胞核内的分布，只有 NDC1 在 HF 中存在差异。此外，在病变组中，我们获得了心室功能参数（LVEDD 和 LVESD）与 Nup160 之间的良好相关性（r=-0.382，p=0.004；r=-0.290，p=0.033）。
本研究表明，在缺血和扩张型人类心脏中，NPC 的特定蛋白（NDC1、Nup160、Nup153 和 Nup93）发生改变。这些与心室功能相关的变化可能伴随着核质转运的改变。因此，我们的发现可能为 HF 管理提供新的思路。
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