自然衰老C57BL/6J雄性小鼠肝脏的定量与乙酰化修饰蛋白质组学特征

目的 获取自然衰老C57BL/6J雄性小鼠肝脏的蛋白质组学与乙酰化修饰蛋白质组学特征。方法 采用串联质谱标签标记定量与液相色谱-串联质谱联用技术,获取生理状况下2月龄与18月龄C57BL/6J雄性小鼠肝脏的蛋白质组学与乙酰化修饰蛋白质组学数据,开展生物信息学分析。结果 蛋白质组学共定量4712个蛋白质,其中,年轻、年老小鼠中有195个差异表达蛋白质;乙酰化修饰蛋白质组学共定量4818个位点,对应1367个蛋白质,其中,年轻、年老小鼠中有113个表达位点有差异,对应76个蛋白质。衰老相关的上调蛋白质主要与脂肪酸代谢、环氧合酶P450途径、药物分解代谢、有机羟基化合物代谢、花生四烯酸代谢等生物学过程相关,下调蛋白质主要与基因沉默、核小体组装、蛋白质异源四聚、干扰素反应、蛋白质-DNA复合物组装等生物学过程相关。伴随衰老上调的乙酰化修饰位点所在蛋白质主要与辅因子代谢、小分子分解代谢、磷酸核糖代谢、核糖核苷酸代谢、嘌呤代谢等生物学过程相关,含下调乙酰化位点的蛋白质主要与含硫化合物代谢、未折叠蛋白反应、氨基酸代谢等生物学过程相关。结论 本研究客观展示了自然衰老C57BL/6J雄性小鼠肝脏的定量和乙酰化修饰蛋白质组学特征,为衰老相关机制探索和干预研究提供了可资参考的数据集。

Proteome and Acetylome Profiling of Livers in C57BL/6J Male Mice during Normal Aging

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.