2013年度森基金研究成果報告書

シミュレーション解析を用いた酸化的ストレスによる赤血球寿命短縮機構の解明

政策・メディア研究科修士２年 先端生命科学プログラム

下 英恵

学籍番号: 81224572

要旨

Human erythrocytes (RBCs) have a lifespan of approximately 120 days, during which they accumulate oxidative damage and eventually become removed from the circulation by the immune system. The clustering of membrane protein band 3 is an essential process in the clearance of damaged and aged RBCs, however the detailed molecular mechanisms of cluster formation remain poorly understood. In this study, we developed a computational model that reproduces the biochemical behavior in RBCs during oxidative treatment, to quantitatively understand the spatiotemporal dynamics and regulatory mechanisms of band 3 clustering. We observed that cluster size and reversibility reflect cellular oxidative capacity, and that strong attractive forces between phosphorylated band 3 greatly contribute to cluster formation. Simulation analyses of clustering with incorporation of a mesh-like structure, implied that compartmentalization of band 3 by spectrin at initial state plays a role in inhibiting cluster formation, and suggested that clustering significantly disrupts the reassembly of the spectrin cytoskeletal network after oxidation. Taken together, our results provide predictive insights on the detailed reaction dynamics of band 3 clustering, its role in RBC senescence, and how it is regulated in vivo.

※本報告書はweb公開であるため，論文発表前の具体的な解析データを除いて作成した

2012年度業

学会発表

・ Shimo H, Nishino T, Arjunan S, Takahashi K, Tomita M. “Computer simulations of oxidative stress induced membrane protein clustering in human erythrocytes”, Kaketsuken The 8^th Aso International Meeting, Aso, Japan