Targeted proteomics for quantification of histone acetylation in Alzheimer's disease.
Targeted proteomics for quantification of histone acetylation in Alzheimer's disease.
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DOI：
10.1002/pmic.201200010
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发表时间：
2012-04
期刊：
影响因子：
3.4
通讯作者：
Kirsch W
中科院分区：
文献类型：
--
作者：
Zhang K;Schrag M;Crofton A;Trivedi R;Vinters H;Kirsch W
通过乙酰化的染色质组蛋白的表观遗传重塑已经成为最近研究的主题，寻找指示晚发性认知丧失的生物标志物。组蛋白乙酰化影响基因转录的调节，并且在特定组蛋白位点处的学习丧失诱导的去乙酰化可能代表记忆丧失和阿尔茨海默病（AD）的生物标志物。选择反应监测（SRM）是近年来发展起来的一种用于复杂生物系统中肽和蛋白质定量分析的新方法。在这份报告中，我们提供的证据表明，SRM为基础的靶向蛋白质组学可以可靠地量化特定的组蛋白乙酰化在AD和控制大脑通过识别H3 K18/K23乙酰化的模式。靶向蛋白质组学分析的结果已经通过蛋白质印迹（WB）分析进行了验证。与LC-MS/MS-TMT（tandem-mass-tag）和WB方法相比，靶向蛋白质组学方法具有更高的通量，因此更适合于临床应用。用这种方法，我们发现组蛋白乙酰化显着降低AD颞叶比老年对照组。靶向蛋白质组学保证增加神经退行性疾病表观遗传学研究的应用。
The epigenetic remodeling of chromatin histone proteins by acetylation has been the subject of recent investigations searching for biomarkers indicative of late onset cognitive loss. Histone acetylations affect the regulation of gene transcription and the loss of learning induced deacetylation at specific histone sites may represent biomarkers for memory loss and Alzheimer’s disease (AD). Selected-reaction-monitoring (SRM) has recently been advanced to quantitate peptides and proteins in complex biological systems. In this report we provide evidence that SRM-based targeted proteomics can reliably quantify specific histone acetylations in both AD and control brain by identifying the patterns of H3 K18/K23 acetylations. Results of targeted proteomics assays have been validated by Western-blot (WB) analysis. As compared with LC-MS/MS-TMT (tandem-mass-tag) and WB methods, the targeted proteomics method has shown higher throughput, therefore, promised to be more suitable for clinical applications. With this methodology we find that histone acetylation is significantly lower in AD temporal lobe than found in aged controls. Targeted proteomics warrants increased application for studying epigenetics of neurodegenerative diseases.
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