Hereditary Hemolytic Anemia: A Proteomic Approach

描述（由申请人提供）：该项目将使用新开发的定量蛋白质组学方法来提供与溶血性贫血相关的蛋白质：蛋白质相互作用的见解。围绕已知红细胞膜骨架突变的临床变异性和非红细胞效应的基本问题仍然没有答案。过去的RBC分析受到系统复杂性和检测低丰度蛋白质的局限性的阻碍。蛋白质组学技术提供了一种偏差较小的方法来全面分析RBC蛋白质相互作用。 将通过串联质谱法分析来自健康小鼠和溶血性贫血小鼠模型的RBC血影制备物。这些分析将有助于确定正常RBC的核心蛋白质组，可以与患病RBC的谱进行比较。假设特定蛋白质的结构和/或丰度的改变将代表可能参与非红系细胞中疾病严重程度和病理生理学的候选物。我们希望对RBC内蛋白质-蛋白质相互作用的更深入了解可以为遗传性溶血性贫血提供新的见解。

DESCRIPTION (provided by applicant): This project will use newly developed quantitative proteomic methodology to provide insights into protein:protein interactions relevant to hemolytic anemia. Fundamental questions remain unanswered surrounding the clinical variability and non-erythroid effects of known RBC membrane skeleton mutations. Past RBC analysis has been hampered by the complexity of the system and limitations in detecting low abundance proteins. Proteomic technology offers a less biased approach to globally profile RBC protein Interactions. Preparations of RBC ghosts from healthy mice and from mouse models of hemolytic anemia will be analyzed by tandem mass spectrometry. These analyses will help define a core set of proteins for the normal RBC that can be compared with the profile for diseased RBCs. It is hypothesized that alterations in the structure and or abundance of specific proteins will represent candidates that may be involved in disease severity and pathophysiology in non-erythroid cells. We hope that a deeper understanding of protein-protein interactions within the RBC can provide new insights into inherited hemolytic anemia.