RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients
RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients
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DOI：
10.1111/j.1742-4658.2007.05717.x
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发表时间：
2007-04-01
期刊：
影响因子：
5.4
通讯作者：
Davies, Kelvin J. A.
中科院分区：
文献类型：
--
作者：
Harris, Cathryn D.;Ermak, Gennady;Davies, Kelvin J. A.
RCAN 1 mRNA至少有两种不同的亚型在正常人脑的神经元细胞中表达。虽然RCAN 1 mRNA在受阿尔茨海默病影响的大脑区域中升高，但尚不清楚该疾病是否影响神经元RCAN 1，或者是否影响其他细胞类型（例如星形胶质细胞或小胶质细胞）。目前还不清楚有多少蛋白质亚型在人脑中表达，以及RCAN 1蛋白在阿尔茨海默病中是否过表达。我们探讨了RCAN 1 -1和RCAN 1 -4 mRNA亚型的表达在各种类型的细胞在正常和阿尔茨海默病尸检样本，使用免疫组织化学和原位杂交相结合的技术。我们发现外显子1和外显子4主要在神经元细胞中表达，并且在星形细胞或小胶质细胞中没有观察到任何一个外显子的显著表达。这在正常和阿尔茨海默病的大脑切片中都是真实的。我们还证明，RCAN 1 -1 mRNA水平约两倍高的神经元阿尔茨海默病患者与非阿尔茨海默病的控制。使用蛋白质印迹法，我们现在表明人脑中表达三种RCAN 1蛋白亚型：RCAN 1 - 1 L、RCAN 1 - 1 S和RCAN 1 -4。我们已经确定RCAN 1 - 1 L的表达水平是RCAN 1 -4的两倍，并且RCAN 1 - 1 S的表达非常少。我们还发现RCAN 1 - 1 L蛋白在阿尔茨海默病患者中过表达，而RCAN 1 -4则没有。根据这些结果，我们得出结论，RCAN 1 -1可能在阿尔茨海默病中发挥作用，而RCAN 1 -4可能具有另一个目的。
At least two different isoforms of RCAN1 mRNA are expressed in neuronal cells in normal human brain. Although RCAN1 mRNA is elevated in brain regions affected by Alzheimer's disease, it is not known whether the disease affects neuronal RCAN1, or if other cell types (e.g. astrocytes or microglia) are affected. It is also unknown how many protein isoforms are expressed in human brain and whether RCAN1 protein is overexpressed in Alzheimer's disease. We explored the expression of both RCAN1-1 and RCAN1-4 mRNA isoforms in various cell types in normal and Alzheimer's disease postmortem samples, using the combined technique of immunohistochemistry and in situ hybridization. We found that both exon 1 and exon 4 are predominantly expressed in neuronal cells, and no significant expression of either of the exons was observed in astocytes or microglial cells. This was true in both normal and Alzheimer's disease brain sections. We also demonstrate that RCAN1-1 mRNA levels are approximately two-fold higher in neurons from Alzheimer's disease patients versus non-Alzheimer's disease controls. Using western blotting, we now show that there are three RCAN1 protein isoforms expressed in human brain: RCAN1-1L, RCAN1-1S, and RCAN1-4. We have determined that RCAN1-1L is expressed at twice the level of RCAN1-4, and that there is very minor expression of RCAN1-1S. We also found that the RCAN1-1L protein is overexpressed in Alzheimer's disease patients, whereas RCAN1-4 is not. From these results, we conclude that RCAN1-1 may play a role in Alzheimer's disease, whereas RCAN1-4 may serve another purpose.