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PMID: 8529130 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex.

Molecular medicine (Cambridge, Mass.) ·Vol. 1 ·No. 6 ·1995-09-00 ·Pages 634-46

Vlassara H, Li YM, Imani F, Wojciechowicz D, Yang Z, Liu FT, Cerami A

Abstract

Advanced glycation end products (AGE), the reactive derivatives of nonenzymatic glucose-protein condensation reactions, are implicated in the multiorgan complications of diabetes and aging. An AGE-specific cellular receptor complex (AGE-R) mediating AGE removal as well as multiple biological responses has been identified. By screening an expression library using antibody against a previously identified component of the AGE-R complex p90, a known partial cDNA clone was isolated with homology to galectin-3, a protein of diverse identity, and member of the galectin family. To explore this unexpected finding, the nature of the interactions between galectin-3 and AGE was studied using intact macrophage-like RAW 264.7 cells, membrane-associated and recombinant galectin-1 through -4, and model AGE-ligands (AGE-BSA, FFI-BSA). Among the members of this family (galectin-1 through 4), recombinant rat galectin-3 was found to exhibit high-affinity 125I-AGE-BSA binding with saturable kinetics (kD 3.5 x 10(7) M-1) that was fully blocked by excess unlabeled naturally formed AGE-BSA or synthetic FFI-BSA, but only weakly inhibited by several known galectin-3 ligands, such as lactose. In addition to the p90, immunoprecipitation with anti-galectin-3, followed by 125I-AGE-BSA ligand blot analysis of RAW 264.7 cell extracts, revealed galectin-3 (28 and 32 kD), as well as galectin-3-associated proteins (40 and 50 kD) with AGE-binding activity. Interaction of galectin-3 with AGE-BSA or FFI-BSA resulted in formation of SDS-, and beta-mercaptoethanol-insoluble, but hydroxylamine-sensitive high-molecular weight complexes between AGE-ligand, galectin-3, and other membrane components. The findings point toward a mechanism by which galectin-3 may serve in the assembly of AGE-R components and in the efficient cell surface attachment and endocytosis by macrophages of a heterogenous pool of AGE moieties with diverse affinities, thus contributing to the elimination of these pathogenic substances.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, Differentiation/analysis,isolation & purification,metabolism Binding, Competitive Carrier Proteins/metabolism Cell Line Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Galectin 3 Glycation End Products, Advanced/metabolism Immunoblotting Iodine Radioisotopes Kinetics Liver/metabolism Macrophages Membrane Glycoproteins/metabolism Mice Molecular Weight Radioligand Assay Rats Receptor for Advanced Glycation End Products Receptors, Immunologic/analysis,isolation & purification,metabolism Recombinant Proteins/analysis,isolation & purification,metabolism
Chemicals
Antibodies, Monoclonal Antigens, Differentiation Carrier Proteins Galectin 3 Glycation End Products, Advanced Iodine Radioisotopes Membrane Glycoproteins Receptor for Advanced Glycation End Products Receptors, Immunologic Recombinant Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Vlassara H
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Li Y M
Imani F
Wojciechowicz D
Yang Z
Liu F T
Cerami A
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Article Info
Journal
Molecular medicine (Cambridge, Mass.)
Abbr.
Mol Med
ISSN
1076-1551
Published
1995-09-00
Pages
634-46
Language
English
Region
England
NLM ID
9501023
PMCID
PMC2229987
Subset
IM
Grants
NIA NIH HHS · AGO-6943 · United States
NIA NIH HHS · AGO-9453 · United States
External Links
PubMed source PMC Full Text View journal details
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