Altering the expression balance of hnRNP C1 and C2 changes the expression of myelination-related genes

Altering the expression balance of hnRNP C1 and C2 changes the expression of myelination-related genes
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DOI:
10.1016/j.psychres.2011.05.043
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发表时间:
2011-12-30
影响因子:
11.3
通讯作者:
Mori, Norio
Mori, Norio
中科院分区:
医学2区
文献类型:
--
作者:
Iwata, Keiko;Matsuzaki, Hideo;Mori, Norio

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有报道称,在精神分裂症患者的死后脑中,hnRNP C1/C2蛋白的表达水平显著降低。在这项研究中,我们研究了hnRNP C变异体hnRNP C1和C2的过表达是否改变了人神经母细胞瘤细胞系SK-N-SH中髓鞘相关基因的表达。在hnRNP C1和C2过表达的细胞中,Quaking(QKI)-6和QKI-7的表达分别显著高于或低于对照组。有趣的是,QKI-5和髓鞘碱性蛋白分别通过过表达hnRNP C2而显著上调或下调。我们的发现首次证明了hnRNP Ca和C2的不同功能,并可能有助于理解这些分子的功能。这些结果提示,精神分裂症患者脑内hnRNP C表达水平的改变可能通过改变QKI亚型和髓鞘碱性蛋白的表达而参与本病的病理生理过程。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
The expression level of hnRNP C1/C2 protein has been reported to be significantly decreased in the postmortem brain of schizophrenic patients. In this study, we investigated whether overexpression of the hnRNP C variants hnRNP C1 and C2 changed the expression of myelination-related genes in the human neuroblastoma cell line SK-N-SH. In both hnRNP C1- and C2-overexpressing cells, the expression of quaking (QKI)-6 and QKI-7 significantly increased or decreased compared to the control, respectively. Intriguingly, QKI-5 and myelin basic protein were markedly up- or down-regulated by overexpressing hnRNP C2, respectively. Our findings are the first to demonstrate distinct functions of hnRNP Ca and C2, and may be helpful in understanding the functions of these molecules. These findings indicate that altered expression levels of hnRNP C in the brain of patients with schizophrenia could be involved in the pathophysiology of this disease through alteration of the QKI isoform and myelin basic protein expression. (C) 2011 Elsevier Ireland Ltd. All rights reserved.