Differential expression of human histone deacetylase mRNAs in response to immune cell apoptosis induction by trichostatin A and butyrate
Differential expression of human histone deacetylase mRNAs in response to immune cell apoptosis induction by trichostatin A and butyrate
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DOI：
10.1006/bbrc.1998.8891
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发表时间：
1998-06-29
影响因子：
3.1
通讯作者：
Gullans, SR
中科院分区：
文献类型：
--
作者：
Dangond, F;Gullans, SR
组蛋白脱乙酰酶(HDACs)和乙酰基转移酶(HATS)对组蛋白的可逆乙酰化在基因转录中起着重要的作用。我们先前的研究表明，在PKA诱导的激活过程中，免疫细胞中的HDAC基因表达上调。然而，关于HDAC抑制剂曲古抑素A(TSA)和丁酸盐对HDAC mRNAs的差异调控知之甚少，这两种药物已知的阻止增殖和诱导凋亡。我们报道，TSA和丁酸的诱导凋亡浓度以不同的方式上调HDAC mRNAs的表达，并与PHA协同作用诱导HDAC的表达，这表明存在独立的HDAC调节机制。此外，我们还发现，HDAC抑制剂诱导的细胞凋亡与Th1淋巴细胞产生γ-干扰素的早期抑制和P53基因的下调有关。我们的发现突出了细胞周期、激活和凋亡相关蛋白与HDACs时间相关表达的动态相互作用，并暗示了这些酶的不同特定作用。(C)1998年学术出版社。
The reversible acetylation of histones by histone deacetylases (HDACs) and acetyltransferases (HATs) plays a fundamental role in gene transcription. We previously showed that HDAC mRNA is upregulated in immune cells upon PKA-induced activation. Little is known, however, about the differential regulation of HDAC mRNAs by the HDAC inhibitors Trichostatin A (TSA) and butyrate, agents known to block proliferation and induce apoptosis. We report that apoptosis-inducing concentrations of TSA and butyrate upregulate the expression of HDAC mRNAs in a differential manner and act synergistically with PHA to induce HDAC expression, suggesting the presence of independent HDAC regulatory mechanisms. Moreover, we show that HDAC inhibitor-induced apoptosis is associated with early abrogation of gamma-IFN production by Th1 lymphocytes and with p53 mRNA downregulation. Our findings highlight the dynamic interplay of cell cycle-, activation- and apoptosis-related proteins in association with time-dependent expression of HDACs and are suggestive of different specific roles for these enzymes. (C) 1998 Academic Press.