title: Comparison of pharmacokinetics between highly and mildly modified AGE proteins in mice.
abstract: We previously demonstrated that RAW 264.7 cells (murine macrophage cell line) recognize highly modified advanced glycation end products (AGE)-bovine serum albumin (BSA) (high-AGE-BSA), which was prepared by incubating BSA with 1600 mmol/L glucose for 40 weeks. In the present study, we prepared mildly modified AGE-BSA (mild-AGE-BSA) and conducted an endocytic uptake study using human monocyte-derived macrophages and Chinese hamster ovary cells which overexpressed such scavenger receptors as CD36, SR-BI (scavenger receptor class B type-I), and LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). Although high-AGE-BSA was significantly recognized by these cells, mild-AGE-BSA did not show any ligand activity to these cells. Furthermore, when 111 In-labeled mild- or high-AGE-BSA was injected into the tail vein of male ddY mice, 111 In-high-AGE-BSA was rapidly cleared from the circulation, with about 80% of the injected 111 In-high-AGE-BSA being eliminated within 5 min. In contrast, the clearance rate of 111 In-mild-AGE-BSA was very slow, similar to the 111 In-native BSA. Taken together, our results indicate that the ligand activity of AGE-BSA to scavenger receptors and those pharmacokinetic properties depend on their rate of modification by AGEs.
authors: Department of Medical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University,Kumamoto 860-8556, Japan. nagai-883@umin.ac.jp
authors: Ryoji
authors: R
authors: Nagai
authors: Katsumi
authors: K
authors: Mera
authors: Yukio
authors: Y
authors: Fujiwara
authors: Mime
authors: M
authors: Nagai
authors: Masaki
authors: M
authors: Otagiri
mesh_terms: D000818:Animals; D017127:Glycation End Products, Advanced / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D011506:Proteins / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine
chemical_list: D017127:Glycation End Products, Advanced; D011506:Proteins; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine