Tilton Ronald G, Haidacher Sigmund J, Lejeune Wanda S, Zhang Xiaoquan, Zhao Yingxin, Kurosky Alexander, Brasier Allan R, Denner Larry
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Proteomics. 2007 May;7(10):1729-42. doi: 10.1002/pmic.200700017.
To understand the spectrum of proteins affected by diabetes and to characterize molecular functions and biological processes they control, we analyzed the renal cortical proteome of db/db mice using 2-DE combined with MALDI-TOF, MALDI-TOF/TOF, and LC-MS/MS. This approach yielded 278 high confidence identifications whose expression levels were significantly increased or decreased >two-fold by diabetes, of which 170 mapped to gene identifiers representing 147 nonredundant proteins. Gene Ontology classification demonstrated that 80% of these proteins modulated physiological functions, 55% involved metabolism, approximately 25% involved carboxylic and organic acid metabolism, 14% involved biosynthesis or catabolism, and 12% involved fatty acid metabolism. Predominant molecular functions were catalytic (61%), oxidoreductase (20%), and transferase (17%) activities, and nucleotide and ATP binding (11-15%). Twenty eight percent of the proteins identified as significantly altered by diabetes were mitochondrial proteins. The top-ranked network described by Ingenuity Pathway Analysis indicated PPARalpha was the most common node of interaction for the numerous enzymes whose expression levels were influenced by diabetes. These differentially regulated proteins create a foundation for a systems biology exploration of molecular mechanisms underlying the pathophysiology of diabetic nephropathy.
为了解受糖尿病影响的蛋白质谱，并表征它们所控制的分子功能和生物学过程，我们使用二维电泳结合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）、串联基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/TOF）和液相色谱-串联质谱（LC-MS/MS）分析了db/db小鼠的肾皮质蛋白质组。这种方法产生了278个高可信度的鉴定结果，其表达水平因糖尿病而显著增加或降低两倍以上，其中170个对应于代表147种非冗余蛋白质的基因标识符。基因本体分类表明，这些蛋白质中有80%调节生理功能，55%参与代谢，约25%参与羧酸和有机酸代谢，14%参与生物合成或分解代谢，12%参与脂肪酸代谢。主要的分子功能是催化活性（61%）、氧化还原酶活性（20%）和转移酶活性（17%），以及核苷酸和ATP结合（11%-15%）。被鉴定为因糖尿病而显著改变的蛋白质中有28%是线粒体蛋白质。 Ingenuity通路分析描述的排名靠前的网络表明，过氧化物酶体增殖物激活受体α（PPARalpha）是众多表达水平受糖尿病影响的酶最常见的相互作用节点。这些差异调节的蛋白质为糖尿病肾病病理生理学潜在分子机制的系统生物学探索奠定了基础。
