Ichibangase Tomoko, Moriya Kyoji, Koike Kazuhiko, Imai Kazuhiro
Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, Japan.
J Proteome Res. 2007 Jul;6(7):2841-9. doi: 10.1021/pr070094c. Epub 2007 Jun 9.
In this post-genome era, a sensitive quantitative method is required for differential profiling analyses of clinical proteomes to understand the disease progress. Here, we adopt the FD-LC-MS/MS method, consisting of fluorogenic derivatization (FD), separation by liquid chromatography (LC), and identification by LC-tandem mass spectrometry (MS/MS), to reveal disease-related proteins in livers of hepatocarcinogenesis in transgenic (Tg) and non-transgenic (NTg) mice at three developmental stages. After 6 months, the expression of apoptosis-related proteins is suppressed. After 12 months, proteins related to respiration, the electron-transfer system, and anti-oxidation are significantly up-regulated. After 16 months, proteins related to defense, beta-oxidation, and apoptosis are significantly suppressed. This fluctuating expression of proteins could explain the progression of hepatocarcinogenesis. The method would be useful for clinical proteomics analysis because of its high resolution, sensitivity, and reproducibility.
在这个后基因组时代,需要一种灵敏的定量方法来对临床蛋白质组进行差异分析,以了解疾病进展。在此,我们采用荧光衍生化(FD)、液相色谱(LC)分离以及液相色谱串联质谱(MS/MS)鉴定的FD-LC-MS/MS方法,来揭示转基因(Tg)和非转基因(NTg)小鼠在三个发育阶段肝癌发生过程中肝脏中的疾病相关蛋白质。6个月后,凋亡相关蛋白的表达受到抑制。12个月后,与呼吸、电子传递系统和抗氧化相关的蛋白显著上调。16个月后,与防御、β-氧化和凋亡相关的蛋白显著受到抑制。蛋白质的这种波动表达可以解释肝癌发生的进程。该方法因其高分辨率、灵敏度和重现性,将对临床蛋白质组学分析有用。