Age-associated changes in synaptic lipid raft proteins revealed by two-dimensional fluorescence difference gel electrophoresis.
Age-associated changes in synaptic lipid raft proteins revealed by two-dimensional fluorescence difference gel electrophoresis.
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DOI：
10.1016/j.neurobiolaging.2008.11.005
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Zaidi, Asma
中科院分区：
文献类型：
--
作者：
Jiang, Lei;Fang, Jianwen;Moore, David S.;Gogichaeva, Natalia V.;Galeva, Nadezhda A.;Michaelis, Mary L.;Zaidi, Asma
脑老化与认知功能的进行性衰退有关，但其分子机制尚不清楚。大脑神经元的功能变化可能是由于对信息处理至关重要的特定蛋白质水平的年龄相关变化。被称为“脂筏”的专门的膜微区包含参与许多信号转导过程的蛋白质复合物。本研究旨在确定突触膜脂筏蛋白质的二维荧光差异凝胶电泳（2D DIGE）分析是否显示筏蛋白水平的年龄依赖性改变。五对年轻和老年大鼠突触膜筏进行DIGE分离，然后进行图像分析和鉴定显着改变的蛋白质。在DIGE凝胶上的1046个匹配点中，94个显示出老年和年轻筏之间的水平存在统计学显著差异，其中87个在老年筏中下降。41个最显著改变的蛋白质（p < 0.03）包括涉及能量代谢、氧化还原稳态和细胞骨架结构的几种突触蛋白。这可能表明，在生物能量平衡和氧化还原稳态的突触筏与脑老化的破坏。通过免疫印迹分析确认代表性鉴定蛋白质的差异水平。我们的研究结果提供了新的途径，在调查的机制，可能有助于改变神经元功能的老化大脑。
Brain aging is associated with a progressive decline in cognitive function though the molecular mechanisms remain unknown. Functional changes in brain neurons could be due to age-related alterations in levels of specific proteins critical for information processing. Specialized membrane microdomains known as ‘lipid rafts’ contain protein complexes involved in many signal transduction processes. This study was undertaken to determine if two-dimensional fluorescence difference gel electrophoresis (2D DIGE) analysis of proteins in synaptic membrane lipid rafts revealed age-dependent alterations in levels of raft proteins. Five pairs of young and aged rat synaptic membrane rafts were subjected to DIGE separation, followed by image analysis and identification of significantly altered proteins. Of 1046 matched spots on DIGE gels, 94 showed statistically significant differences in levels between old and young rafts, and 87 of these were decreased in aged rafts. The 41 most significantly altered (p < 0.03) proteins included several synaptic proteins involved in energy metabolism, redox homeostasis, and cytoskeletal structure. This may indicate a disruption in bioenergetic balance and redox homeostasis in synaptic rafts with brain aging. Differential levels of representative identified proteins were confirmed by immunoblot analysis. Our findings provide novel pathways in investigations of mechanisms that may contribute to altered neuronal function in aging brain.
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