Department of Cell and Molecular Biology, Biomedical Center, Box 596, Uppsala University, SE-751 24 Uppsala, Sweden.
Proteome Sci. 2007 Nov 27;5:19. doi: 10.1186/1477-5956-5-19.
Despite major recent advances in the understanding of peroxisomal functions and how peroxisomes arise, only scant information is available regarding this organelle in cellular aging. The aim of this study was to characterize the changes in the protein expression profile of aged versus young liver and kidney peroxisome-enriched fractions from mouse and to suggest possible mechanisms underlying peroxisomal aging. Peroxisome-enriched fractions from 10 weeks, 18 months and 24 months C57bl/6J mice were analyzed by quantitative proteomics.
Peroxisomal proteins were enriched by differential and density gradient centrifugation and proteins were separated by two-dimensional electrophoresis (2-DE), quantified and identified by mass spectrometry (MS). In total, sixty-five proteins were identified in both tissues. Among them, 14 proteins were differentially expressed in liver and 21 proteins in kidney. The eight proteins differentially expressed in both tissues were involved in beta-oxidation, alpha-oxidation, isoprenoid biosynthesis, amino acid metabolism, and stress response. Quantitative proteomics, clustering methods, and prediction of transcription factors, all indicated that there is a decline in protein expression at 18 months and a recovery at 24 months.
These results indicate that some peroxisomal proteins show a tissue-specific functional response to aging. This response is probably dependent on their differential regeneration capacity. The differentially expressed proteins could lead several cellular effects: such as alteration of fatty acid metabolism that could alert membrane protein functions, increase of the oxidative stress and contribute to decline in bile salt synthesis. The ability to detect age-related variations in the peroxisomal proteome can help in the search for reliable and valid aging biomarkers.
尽管近年来对过氧化物酶体功能及其发生方式的理解有了重大进展，但关于细胞衰老过程中该细胞器的信息却很少。本研究旨在描述来自年轻和衰老的小鼠肝脏和肾脏过氧化物酶体富集部分的蛋白质表达谱的变化，并提出过氧化物酶体衰老的可能机制。使用定量蛋白质组学分析了 10 周、18 个月和 24 个月 C57bl/6J 小鼠的过氧化物酶体富集部分。
通过差速和密度梯度离心富集过氧化物酶体蛋白，并通过二维电泳（2-DE）分离蛋白，通过质谱（MS）定量和鉴定。在这两种组织中，共鉴定出 65 种蛋白质。其中，14 种在肝脏中差异表达，21 种在肾脏中差异表达。在这两种组织中差异表达的 8 种蛋白质参与β-氧化、α-氧化、异戊二烯生物合成、氨基酸代谢和应激反应。定量蛋白质组学、聚类方法和转录因子的预测都表明，18 个月时蛋白质表达下降，24 个月时恢复。
这些结果表明，一些过氧化物酶体蛋白对衰老表现出组织特异性的功能反应。这种反应可能取决于它们不同的再生能力。差异表达的蛋白质可能会导致几种细胞效应：例如改变脂肪酸代谢，从而改变膜蛋白功能；增加氧化应激，导致胆汁盐合成减少。检测过氧化物酶体蛋白质组中与年龄相关的变化的能力有助于寻找可靠和有效的衰老生物标志物。
