Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex
Open accessAbstract
Background 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.Materials and methods 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).Results 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.Conclusions 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.
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TNF-a also mediates insulin resistance via p38 MAPK activation interfering with the IRS-PI3K-Akt pathway.
“TNF-a mediates insulin resistance also via the activation of p38 mitogen-activated protein kinase (MAPK) which interferes with the IRS -phosphatidylinositol 3-kinase -Akt pathway (129) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [129]
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- Authors
- Vlassara, H., Li, Y. M., Imani, F., Wojciechowicz, D., Yang, Z., Liu, F.-T., & Cerami, A.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Molecular Medicine
- Published
- 1995-09
- Volume
- 1
- Issue
- 6
- Pages
- 634-646
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC2229987
- OpenAlex
- W1547902391
- Cited by
- 421
- References
- 47
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 15 · 2020: 14 · 2019: 9 · 2018: 10 · 2017: 11 · 2016: 17 · 2015: 15 · 2014: 19 · 2013: 16 · 2012: 18
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michigan State University
- National Institutes of Health
- College of Engineering, Michigan State University
- University of California, San Francisco
- National Institute on Aging (AGO-6943, AGO-9453)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- galectin-3, advanced glycation end products, P90, macrophages, endocytosis, diabetes complications, aging, high-affinity binding
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Antibodies, Monoclonal, Antigens, Differentiation, Binding, Competitive, Carrier Proteins, Cell Line, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Iodine Radioisotopes, Kinetics, Liver, Macrophages, Membrane Glycoproteins, Molecular Weight, Radioligand Assay, Receptors, Immunologic, Recombinant Proteins, Immunoblotting, Glycation End Products, Advanced, Galectin 3, Mice, Rats
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