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 suggest ed to be an AGE-receptor. To examine this possibility, we prepared CHO cell s overexpressing human galectin-3 (galectin-3-CHO cells). Galectin-3-CHO ce lls showed a specific and saturable binding to I-125-AGE-BSA with Kd of 3.1 mug/ml. I-125-AGE-BSA was endocytosed by galectin-3-CHO cells and underwen t lysosomal degradation. The endocytosis of I-125-AGE-BSA was inhibited not only by unlabeled AGE-BSA but also by acetylated LDL and oxidized LDL, lig ands for the scavenger receptor family. Furthermore, I-125-oxidized LDL and I-125-acetylated LDE were actively endocytosed by galectin-3-CHO cells and the incubation with acetyl-LDL led to intracellular accumulation of choles teryl esters, indicating the role of galectin-3 in endocytosis of AGE-prote ins and modified LDLs. Since galectin-3 was localized and upregulated in fo am 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. (C) 2001 Academic Press.