Selective regulation of class I and class II histone deacetylases expression by inhibitors of histone deacetylases in cultured mouse neural cells
Selective regulation of class I and class II histone deacetylases expression by inhibitors of histone deacetylases in cultured mouse neural cells
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DOI：
10.1016/j.neulet.2004.04.087
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发表时间：
2004-07-15
影响因子：
2.5
通讯作者：
Reeben, M
中科院分区：
文献类型：
--
作者：
Ajamian, F;Salminen, A;Reeben, M
研究了HDAC抑制剂、丁酸钠和曲古霉素A对小鼠神经母细胞瘤神经-2a和小胶质细胞N9细胞培养后10种组蛋白去乙酰化酶（HDAC1-10） mrna的表达，以阐明HDAC抑制剂是否影响HDAC本身的基因表达。Northern blot分析显示，与未治疗的细胞相比，药物治疗后HDAC 1、-3、-5和-6的mRNA水平升高了2至4倍，而HDAC2和-7的mRNA水平没有显著变化。在神经-2a和N9细胞中，HDAC5和-6 mRNA的表达增加最多，而HDAC4 mRNA的表达仅在N9小胶质细胞系中显著增加，而在神经-2a细胞中没有。免疫细胞化学检查证实hdac蛋白水平的变化与其mRNA水平的变化相似。抑制几种HDAC的生化活性后，其表达水平存在自调节反馈回路，使几种HDAC基因加入到HDAC抑制剂调节的基因列表中。2004爱思唯尔爱尔兰有限公司版权所有。
The expression of 10 histone deacetylases (HDAC1-10) mRNAs in mouse neuroblastoma Neuro-2a and microglia N9 cell cultures after treatment by inhibitors of HDACs, sodium butyrate and trichostatin A was studied to elucidate whether HDAC inhibitors affect the gene expression of HDACs themselves. Northern blot analysis demonstrated two- to four-fold elevated levels of mRNAs for HDAC 1, -3, -5, and -6 after drug treatment in comparison with untreated cells, while mRNA levels for HDAC2 and -7 did not change significantly. In both Neuro-2a and N9 cells the highest increase was observed for HDAC5 and -6 mRNA, whereas, HDAC4 had a prominent increase in mRNA levels after drug treatment only in N9 microglia cell line but not in Neuro-2a. Immunocytochemical examination confirmed that changes in protein levels of HDACs were similar to changes in their mRNA levels. There exists an auto-regulatory feedback loop to the expression levels of several HDACs after inhibition of their biochemical activity, adding several HDAC genes to the list of genes regulated by HDAC inhibitors. (C) 2004 Elsevier Ireland Ltd. All rights reserved.