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研究発表を行った学会；
・2nd Asian-Pacific ISSX Meeting
　2007年5月11日〜13日（上海）

タイトル；The pharmacokinetic properties of AGE-proteins is dependent on their rate of modification by AGEs.
　
発表者；　米良　克美　氏
　　　（熊本大学　大学院薬学教育部　薬物動態制御学分野）
Abstract；
Cellular interaction with proteins modified with advanced glycation end-products (AGEs) is believed to induce several biological responses, which are involved in the development of diabetic vascular complications. We previously demonstrated that RAW 264.7 cells, a murine macrophage cell line, recognize highly-modified AGE-bovine serum albumin (high-AGE-BSA) which was prepared by incubating BSA with 1600 mM glucose for 40 weeks. Our subsequent study, however, showed that mildly-modified AGE-BSA (mild-AGE-BSA) which was prepared by incubating BSA with 50 mM glucose for 24 weeks did not show any ligand activity to the cells. To clarify the ligand activity of mild-AGE-BSA to scavenger receptors, we conducted endocytic uptake study using human monocyte-derived macrophages and Chinese hamster ovary cells overexpressing scavenger receptors such as CD36, SR-BI (scavenger receptor class B type-I), LOX-1 (lectin-like oxidized LDL receptor-1). Although high-AGE-BSA was significantly recognized by these cells, mild-AGE-BSA did not show any ligand activity to the cells. Furthermore, we also conducted the pharmacokinetic analysis of AGE-BSA in order to evaluate its ligand activity to scavenger receptors in vivo. The radioactivity of 111In-high-AGE-BSA was rapidly cleared from the circulation, with about 80% of the injected 111In-high-AGE-BSA being eliminated within 5 min, and 60% of injected radioactivity accumulated in the liver. In contrast, the clearance rate of 111In-mild-AGE-BSA was very slow as 111In-native BSA. Taken together, our results indicate that ligand activity of AGE-BSA to scavenger receptors and its pharmacokinetic properties depend on their rate of modification by AGE, and we should carefully prepare the AGE-proteins in vitro to clarify the physiological significance of the interaction between the AGE-receptors and AGE-proteins.