Age-related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects
Age-related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects
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DOI：
10.1111/j.1471-4159.2008.05762.x
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Ruano, Diego
中科院分区：
文献类型：
--
作者：
Gavilan, M. Paz;Castano, Angelica;Ruano, Diego
在中枢神经系统中的蛋白酶体活性的变化已被描述在老化。然而，实际上缺乏对所有蛋白酶体亚基的详细研究。我们已经分析了，在体内，海马蛋白酶体的分子组成的年龄相关的修改。我们发现，免疫蛋白酶体/蛋白酶体的比例增加，在老龄海马。低分子量蛋白（LMP）7/β（5i）亚基的加工在年轻的海马中几乎不存在，但在老年动物中增加。在这些修饰的潜在因素中，我们评估了神经炎症和转录因子Zif 268。脂多糖（LPS）诱导的幼年大鼠神经炎症，上调免疫蛋白酶体亚单位的表达，并增加LMP 7/β（5i）蛋白的加工。此外，通过液相色谱分析，在年轻的LPS注射动物和老年大鼠中，细胞肽的疏水性增加，表明包括LMP 7/β（5i）亚基的免疫蛋白酶体可以至少部分地解释这种修饰。此外，转录因子Zif 268的mRNA表达在老年海马和年轻LPS注射动物中均降低，该转录因子Zif 268通过与启动子区域内的序列结合来下调免疫蛋白酶体亚基LMP 7/β（5i）。最后，我们发现，在年轻动物的空间记忆训练，Zif 268的表达增加的情况下，修改的组成和催化亚基的mRNA表达以相反的方式。根据目前的数据，我们提出，海马免疫蛋白酶体含量的年龄相关性增加主要是因为与衰老相关的神经炎症过程。
Alterations in the proteasome activity in the CNS have been described during aging. However, a detailed study of all proteasome subunits is actually lacking. We have analyzed, in vivo, the age-related modifications in the molecular composition of hippocampal proteasomes. We found that the immunoproteasome/proteasome ratio was increased in aged hippocampus. The processing of the low-molecular-mass protein (LMP)7/beta(5i) subunit, practically absent in young hippocampus, was increased in aged animals. Among the potential factors underlying these modifications we evaluated the neuroinflammation and the transcription factor Zif268. Lipopolysaccharide (LPS)-induced neuroinflammation in young rats, up-regulated the expression of immunoproteasome subunits and increased the processing of the LMP7/beta(5i) protein. Moreover, the hydrophobicity of cellular peptides, analyzed by liquid chromatography, increased in both, young LPS-injected animals and aged rats, suggesting that immunoproteasomes including the LMP7/beta(5i) subunit could, at least in part, account for this modification. Also, the mRNA expression of the transcription factor Zif268, which down-regulates the immunoproteasome subunit LMP7/beta(5i) by binding to sequences within the promoter regions, was decreased in both, aged hippocampus and young LPS-injected animals. Finally, we found that spatial memory training in young animals, a situation in which the expression of Zif268 is increased, modified the mRNA expression of the constitutive and catalytic subunits in an opposite manner. Based on present data, we propose that the age-related increases in the content of hippocampal immunoproteasome is mostly because of neuroinflammatory processes associated to aging.