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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND).
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HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND).

机译：HIV-1 Tat上调人神经元中组蛋白脱乙酰基酶2（HDAC2）的表达：对HIV相关的神经认知障碍（HAND）的影响。

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摘要

Histone deacetylases (HDACs) play a pivotal role in epigenetic regulation of transcription and homeostasis of protein acetylation in histones and other proteins involved in chromatin remodeling. Histone hypoacetylation and transcriptional dysfunction have been shown to be associated with a variety of neurodegenerative diseases. More recently, neuron specific overexpression of HDAC2 has been shown to modulate synaptic plasticity and learning behavior in mice. However, the role of HDAC2 in development of HIV-associated neurocognitive disorders (HAND) is not reported. Herein we report that HIV-1 Tat protein upregulate HDAC2 expression in neuronal cells leading to transcriptional repression of genes involved in synaptic plasticity and neuronal function thereby contributing to the progression of HAND. Our results indicate upregulation of HDAC2 by Tat treatment in dose and time dependant manner by human neuroblastoma SK-N-MC cells and primary human neurons. Further, HDAC2 overexpression was associated with concomitant downregulation in CREB and CaMKIIa genes that are known to regulate neuronal activity. These observed effects were completely blocked by HDAC2 inhibition. These results for the first time suggest the possible role of HDAC2 in development of HAND. Therefore, use of HDAC2 specific inhibitor in combination with HAART may be of therapeutic value in treatment of neurocognitive disorders observed in HIV-1 infected individuals.
机译：组蛋白脱乙酰基酶（HDAC）在表观遗传调控组蛋白和其他与染色质重塑相关的蛋白中的乙酰化过程中起着举足轻重的作用。组蛋白低乙酰化和转录功能障碍已被证明与多种神经退行性疾病有关。最近，HDAC2的神经元特异性过表达已被证明可调节小鼠的突触可塑性和学习行为。但是，尚未报道HDAC2在与HIV相关的神经认知障碍（HAND）发生中的作用。本文中，我们报道HIV-1 Tat蛋白上调神经元细胞中的HDAC2表达，导致涉及突触可塑性和神经元功能的基因的转录抑制，从而促进HAND的发展。我们的结果表明，人神经母细胞瘤SK-N-MC细胞和原代人神经元通过Tat处理以剂量和时间依赖性方式上调HDAC2。此外，HDAC2的过表达与CREB和CaMKIIa基因的随之下调有关，这些基因已知可调节神经元的活性。这些观察到的作用被HDAC2抑制完全阻断。这些结果首次暗示了HDAC2在HAND的发展中的可能作用。因此，将HDAC2特异性抑制剂与HAART结合使用可能具有治疗HIV-1感染者所见的神经认知障碍的治疗价值。

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