Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Universitätsmedizin Greifswald, Friedrich-Ludwig-Jahn-Str. 15A, 17487 Greifswald, Germany.
Abteilung Molekulare Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Proteome Sci. 2013 Jul 1;11:29. doi: 10.1186/1477-5956-11-29. eCollection 2013.
A.BY/SnJ mice are used to study pathological alterations in the heart due to enteroviral infections. Since age is a well-known factor influencing the susceptibility of mice to infection, response to stress and manifestation of cardiovascular diseases, the myocardial proteome of A.BY/SnJ mice aged 1 and 4 months was comparatively studied using two dimensional-differential in-gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS).
Complementary analyses by 2D-DIGE and gel-free LC-MS/MS revealed 96 distinct proteins displaying age associated alterations in their levels. Proteins related to protein transport, and transport chain, lipid metabolism and fatty acid transport showed significant changes in 4 months old mouse hearts compared to juvenile hearts. Proteins involved in lipid metabolism and transport were identified at significantly higher levels in older mice and dysregulation of proteins of the respiratory transport chain were observed.
The current proteomics study discloses age dependent changes occurring in the hearts already in young mice of the strain A.BY/SnJ. Besides alterations in protein transport, we provide evidence that a decrease of ATP synthase in murine hearts starts already in the first months of life, leading to well-known low expression levels manifested in old mice thereby raising the possibility of reduced energy supply. In the first few months of murine life this seems to be compensated by an increased lipid metabolism. The functional alterations described should be considered during experimental setups in disease related studies.
A.BY/SnJ 小鼠被用于研究肠道病毒感染引起的心脏病理学改变。由于年龄是影响小鼠易感性、对压力的反应和心血管疾病表现的一个已知因素，因此使用二维差异凝胶电泳（2D-DIGE）和液相色谱串联质谱（LC-MS/MS）比较研究了 1 月龄和 4 月龄 A.BY/SnJ 小鼠的心肌蛋白质组。
通过 2D-DIGE 和无胶 LC-MS/MS 的互补分析，发现 96 种不同的蛋白质显示出与其水平相关的年龄变化。与蛋白质转运、转运链、脂质代谢和脂肪酸转运相关的蛋白质在 4 月龄小鼠心脏中与幼年心脏相比发生了显著变化。在老年小鼠中，参与脂质代谢和转运的蛋白质水平明显升高，并且观察到呼吸转运链蛋白的失调。
本研究通过蛋白质组学揭示了 A.BY/SnJ 小鼠心脏中已经存在的年龄依赖性变化。除了蛋白质转运的改变外，我们还提供了证据表明，在小鼠心脏中 ATP 合酶的减少早在生命的头几个月就开始了，导致在老年小鼠中表现出众所周知的低表达水平，从而增加了能量供应减少的可能性。在小鼠生命的最初几个月，这似乎通过增加脂质代谢得到了补偿。在疾病相关研究的实验设计中应考虑描述的功能改变。
