小鼠脑蛋白质组中与年龄相关的蛋白质折叠稳定性差异的发现。
Discovery of Age-Related Protein Folding Stability Differences in the Mouse Brain Proteome.
作者信息
Roberts Julia H, Liu Fang, Karnuta Jaret M, Fitzgerald Michael C
机构信息
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
出版信息
J Proteome Res. 2016 Dec 2;15(12):4731-4741. doi: 10.1021/acs.jproteome.6b00927. Epub 2016 Nov 17.
Abstract
Described here is the application of thermodynamic stability measurements to study age-related differences in the folding and stability of proteins in a rodent model of aging. Thermodynamic stability profiles were generated for 809 proteins in brain cell lysates from mice, aged 6 (n = 7) and 18 months (n = 9) using the Stability of Proteins from Rates of Oxidation (SPROX) technique. The biological variability of the protein stability measurements was low and within the experimental error of SPROX. A total of 83 protein hits were detected with age-related stability differences in the brain samples. Remarkably, the large majority of the brain protein hits were destabilized in the old mice, and the hits were enriched in proteins that have slow turnover rates (p < 0.07). Furthermore, 70% of the hits have been previously linked to aging or age-related diseases. These results help validate the use of thermodynamic stability measurements to capture relevant age-related proteomic changes and establish a new biophysical link between these proteins and aging.
摘要
本文描述了热力学稳定性测量在衰老啮齿动物模型中研究蛋白质折叠和稳定性的年龄相关差异方面的应用。使用氧化速率蛋白质稳定性（SPROX）技术，对6个月大（n = 7）和18个月大（n = 9）小鼠的脑细胞裂解物中的809种蛋白质生成了热力学稳定性图谱。蛋白质稳定性测量的生物学变异性较低，且在SPROX的实验误差范围内。在脑样本中检测到总共83种与年龄相关的稳定性差异的蛋白质。值得注意的是，绝大多数脑蛋白在老年小鼠中不稳定，并且这些命中的蛋白质富含周转率低的蛋白质（p < 0.07）。此外，70%的命中蛋白质此前已与衰老或与年龄相关的疾病相关联。这些结果有助于验证使用热力学稳定性测量来捕捉相关的年龄相关蛋白质组变化，并在这些蛋白质与衰老之间建立新的生物物理联系。
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