The ligand activity of AGE-proteins to scavenger receptors is dependent on their rate of modification by AGEs.
The cellular interaction of proteins modified with advanced glycation end-products (AGEs) is believed to induce several different biological responses, which are involved in the development of diabetic vascular complications. We report here that the ratio of protein glycation is implicated in its ligand activity to scavenger receptors. Although highly-modified AGE-bovine serum albumin (high-AGE-BSA) was significantly recognized by human monocyte-derived macrophages and Chinese hamster ovary cells which overexpress such scavenger receptors as CD36, SR-BI (scavenger receptor class B type-I), and LOX-1 (Lectin-like Ox-LDL receptor-1), the mildly-modified-AGE-BSA (mild-AGE-BSA) did not show any ligand activity to these cells. Furthermore, when (111)In-labeled high- or mild-AGE-BSA were injected into the tail vein of mice, the high-AGE-BSA was rapidly cleared from the circulation whereas the clearance rate of the mild-AGE-BSA was very slow, similar to the native BSA. These results demonstrate the first evidence that the ligand activity of the AGE-proteins to the scavenger receptors and its pharmacokinetic properties depend on their rate of modification by AGEs, 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.
Nagai
Ryoji
R
Department of Medical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Honjo, 1-1-1, Kumamoto 860-8556, Japan. nagai-883@umin.ac.uk
Mera
Katsumi
K
Nakajou
Keisuke
K
Fujiwara
Yukio
Y
Iwao
Yasunori
Y
Imai
Hiroki
H
Murata
Toshinori
T
Otagiri
Masaki
M
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D003459:Crystallins / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D051116:Receptors, Scavenger / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution
D000447:Aldehydes; D003459:Crystallins; D017127:Glycation End Products, Advanced; D008024:Ligands; D051116:Receptors, Scavenger; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C048496:N(6)-carboxymethyllysine; D008239:Lysine