The role of galectin-3 in endocytosis of advanced glycation end products and modified low density lipoproteins.
Galectin-3, a member of beta-galactoside-binding lectin family, is suggested to be an AGE-receptor. To examine this possibility, we prepared CHO cells overexpressing human galectin-3 (galectin-3-CHO cells). Galectin-3-CHO cells showed a specific and saturable binding to (125)I-AGE-BSA with Kd of 3.1 microg/ml. (125)I-AGE-BSA was endocytosed by galectin-3-CHO cells and underwent lysosomal degradation. The endocytosis of (125)I-AGE-BSA was inhibited not only by unlabeled AGE-BSA but also by acetylated LDL and oxidized LDL, ligands for the scavenger receptor family. Furthermore, (125)I-oxidized LDL and (125)I-acetylated LDL were actively endocytosed by galectin-3-CHO cells and the incubation with acetyl-LDL led to intracellular accumulation of cholesteryl esters, indicating the role of galectin-3 in endocytosis of AGE-proteins and modified LDLs. Since galectin-3 was localized and up-regulated in foam cells at human atherosclerotic lesions, the present results suggest that galectin-3 plays an important role in formation of atherosclerotic lesions in vivo, by modulating endocytic uptake of AGE-proteins and modified LDLs.
Zhu
W
W
Department of Biochemistry, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto, 860-0811, Japan.
Sano
H
H
Nagai
R
R
Fukuhara
K
K
Miyazaki
A
A
Horiuchi
S
S
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D037502:Galectin 3; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D014162:Transfection
D000943:Antigens, Differentiation; D037502:Galectin 3; D017127:Glycation End Products, Advanced; D008024:Ligands; D008077:Lipoproteins, LDL; D012709:Serum Albumin; D010100:Oxygen