Central Laboratory, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
J Proteome Res. 2013 Sep 6;12(9):4064-73. doi: 10.1021/pr4004079. Epub 2013 Aug 20.
Suberoylanilide hydroxamic acid (SAHA) is a well-known pan HDAC inhibitor, and its clinical application (Vorinostat) has been demonstrated to treat nonsmall cell lung cancer (NSCLS). Nevertheless, the impact of SAHA treatment on histone lysine acetylation and proteome in NSCLS cells still need further elucidate. In NSCLS A549 cells, by using stable isotope labeling for cell culture (SILAC)-based quantitative proteomics, biochemistry assay, and bioinformatic analysis, here we for the first time comprehensively identified and quantified histone lysine acetylation in A549 cells toward SAHA treatment. Despite the fact that SAHA treatment significantly increased histone lysine acetylation in specific sites, unexpectedly, some important "histone markers" showed markedly decreased acetylation level. Further quantitative proteome studies showed that among totally quantifiable 2818 nonredundant proteins, 1355 proteins were with increased level and 1463 with decreased level in response to SAHA treatment. Bioinformatic analysis further revealed that those quantifiable proteins were mainly involved in multiple biological functions and metabolic and enzyme-regulated pathways as well as protein complexes. By establishing the link between histone modification and whole proteome in response to SAHA treatment in NSCLS cells, this study therefore may deepen our understanding of HDAC inhibitor-mediated cancer therapeutics.
琥珀酰亚胺基戊二酰胺（SAHA）是一种著名的组蛋白去乙酰化酶（HDAC）抑制剂，其临床应用（伏立诺他）已被证明可治疗非小细胞肺癌（NSCLS）。然而，SAHA 处理对 NSCLS 细胞组蛋白赖氨酸乙酰化和蛋白质组的影响仍需要进一步阐明。在 NSCLS A549 细胞中，通过使用稳定同位素标记的细胞培养（SILAC）-基于定量蛋白质组学、生物化学测定和生物信息学分析，我们首次全面鉴定和定量了 SAHA 处理对 A549 细胞的组蛋白赖氨酸乙酰化。尽管 SAHA 处理显著增加了特定位点的组蛋白赖氨酸乙酰化，但令人惊讶的是，一些重要的“组蛋白标记”显示出明显降低的乙酰化水平。进一步的定量蛋白质组学研究表明，在总共可定量的 2818 个非冗余蛋白质中，有 1355 个蛋白质的水平因 SAHA 处理而增加，1463 个蛋白质的水平因 SAHA 处理而降低。生物信息学分析进一步表明，这些可定量的蛋白质主要涉及多种生物学功能以及代谢和酶调节途径以及蛋白质复合物。通过在 NSCLS 细胞中建立组蛋白修饰与整个蛋白质组对 SAHA 处理的反应之间的联系，本研究因此可能加深我们对 HDAC 抑制剂介导的癌症治疗的理解。
