Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Alzheimers Dis. 2011;23(4):641-54. doi: 10.3233/JAD-2010-101389.
In order to discover and identify the key protein biomarkers in the aging process, we performed a differential proteomic analysis of hippocampus and cortex in 5- and 15-month old senescence-accelerated mouse prone 8 (SAMP8) as well as in control strain SAM/resistant 1 (SAMR1). Using 2-DE combined with MALDI TOF/TOF mass spectrometry, about 1700 protein spots were isolated, and three groups of differentially expressed proteins were identified. The first group contained the strain-specific and non-age-related differential proteins that were differentially expressed in SAMP8 compared with SAMR1 mice. The changes might be implicated in the genetic difference between SAMP8 and SAMR1 mice; specifically, the proteins ubiquitin carboxyl-terminal esterase L3, mitofilin, adenylate kinase 4, and an unnamed protein product (gi|12847201). The proteins in the second group were age-specific, which were differentially expressed between 5- and 15-month old SAM mice. Those proteins are particularly interesting since the changes were aging-related and some of them were previously reported to be expressed in Alzheimer's disease patients. These proteins included N-myc downstream regulated gene 2, enolase 2, Cu/Zn superoxide dismutase, myosin, and two unnamed protein products (gi|74214304 and gi|74178239). The protein in the third group was SAMP8 specific-age-related protein, which was identified as heme binding protein 1. The present study provides new information about SAMP8 specific and aging-related protein changes in brain. Further investigations will be performed to reveal the significance of these proteins in brain aging process and the potential roles as biomarkers for effective diagnosis and therapy.
为了发现和鉴定衰老过程中的关键蛋白质生物标志物，我们对 5 个月和 15 个月大的快速老化 SAMP8 小鼠以及对照品系 SAMR1 中的海马体和皮质进行了差异蛋白质组学分析。使用 2-DE 结合 MALDI-TOF/TOF 质谱，分离出约 1700 个蛋白质斑点，并鉴定了三组差异表达的蛋白质。第一组包含品系特异性和非年龄相关的差异蛋白，这些蛋白在 SAMP8 与 SAMR1 小鼠之间差异表达。这些变化可能与 SAMP8 和 SAMR1 小鼠之间的遗传差异有关；具体来说，这些蛋白包括泛素羧基末端酯酶 L3、线粒体蛋白、腺苷酸激酶 4 和一个未命名的蛋白质产物（gi|12847201）。第二组蛋白是年龄特异性的，它们在 5 个月和 15 个月大的 SAM 小鼠之间差异表达。这些蛋白特别有趣，因为它们的变化与衰老有关，其中一些蛋白以前在阿尔茨海默病患者中被报道表达。这些蛋白包括 N-myc 下游调节基因 2、烯醇酶 2、Cu/Zn 超氧化物歧化酶、肌球蛋白和两个未命名的蛋白质产物（gi|74214304 和 gi|74178239）。第三组蛋白是 SAMP8 特异性年龄相关蛋白，被鉴定为血红素结合蛋白 1。本研究为大脑中 SAMP8 特异性和衰老相关蛋白变化提供了新信息。进一步的研究将揭示这些蛋白在大脑衰老过程中的意义以及作为有效诊断和治疗的生物标志物的潜在作用。
