A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells.
A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells.
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DOI：
10.1186/1750-1326-6-9
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发表时间：
2011-01-21
影响因子：
15.1
通讯作者：
Liu QY
中科院分区：
文献类型：
--
作者：
Lei JX;Cassone CG;Luebbert C;Liu QY
多种生物学过程中的分子变化有助于慢性神经退行性疾病如迟发性阿尔茨海默病（LOAD）的发展。为了发现这些变化如何在基因表达水平上反映出来，我们使用了一种基于消减转录的mRNA扩增方法来鉴定在阿尔茨海默病（AD）患者大脑中改变表达水平的新基因。在AD大脑中表达水平改变的基因中，有一种转录本编码一种新的蛋白质SDIM 1，它含有146个氨基酸，包括一个典型的信号肽和两个跨膜结构域。在这里，我们研究了它的生物化学特性和神经保护/神经变性中的假定作用。另外的AD和对照死后人脑的QRT-PCR分析显示，SDIM 1转录物在所有AD脑中确实显著下调。SDIM 1在NT 2神经元中比星形胶质细胞更丰富，并且存在于整个细胞质和神经过程中，但不在细胞核中。在NT 2神经元中，它对模拟可能导致AD大脑神经变性的损伤的应激条件高度反应。例如，SDIM 1在氧-葡萄糖剥夺（OGD）后2小时显著下调，尽管16小时后恢复，并且与未处理的NT 2神经元相比也出现显著上调。SDIM 1在神经前体细胞中的过表达提高了细胞在损伤性损伤后的存活能力，其下调加速了OGD诱导的细胞死亡。酵母双杂交筛选和免疫共沉淀方法揭示，在体外和体内，SDIM 1和DNAJB 4，热休克蛋白hsp 40同源物，最近被称为细胞凋亡的增强剂，也相互作用与μ阿片受体在人脑之间的相互作用。单独过表达DNAJB 4显著降低细胞活力，SDIM 1共过表达能够减弱DNAJB 4引起的细胞死亡，这表明SDIM 1与DNAJB 4的结合可能螯合DNAJB 4，从而增加细胞活力。总之，我们已经确定了一个小的膜蛋白，这是下调AD大脑和神经元细胞暴露于有害的侮辱。它促进存活的能力及其与DNAJB 4的相互作用表明它可能在脑细胞存活和/或受体运输中发挥非常特定的作用。
Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD). To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD) patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration. QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD), though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both in vitro and in vivo, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death caused DNAJB4, suggesting that the binding of SDIM1 to DNAJB4 might sequester DNAJB4, thus increasing cell viability. Taken together, we have identified a small membrane protein, which is down regulated in AD brains and neuronal cells exposed to injurious insults. Its ability to promote survival and its interaction with DNAJB4 suggest that it may play a very specific role in brain cell survival and/or receptor trafficking.
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影响因子：
15.1
作者：
Liu QY;Lei JX;Sikorska M;Liu R
通讯作者：
Liu R
影响因子：
7.5
作者：
Walker, PR;Smith, B;Lach, B
通讯作者：
Lach, B
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
影响因子：
4.2
作者：
Colangelo, V;Schurr, J;Lukiw, WJ
通讯作者：
Lukiw, WJ
影响因子：
2.9
作者：
Liu, QY;Pandey, S;Sikorska, M
通讯作者：
Sikorska, M