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Short-chain aldehyde-derived ligands for RAGE and their actions on endothelial cells
- Source :
- Diabetes Research and Clinical Practice. 77:S30-S40
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- The formation and accumulation of advanced glycation endproducts (AGE) have been implicated in the development of diabetic vascular complications. Their biological responses are known to be mediated by the receptor for AGE (RAGE). Recently, AGE have been proposed to be derived not only from the classical Maillard reaction but also from other pathways of sugar autoxidation and metabolism. Here, we report the identification of glyceraldehydes (Gcer)- and glycolaldehyde (Gcol)-derived AGE as RAGE ligands and their presence in vivo. The apparent dissociation constants assessed by surface-plasmon resonance (SPR) analysis with purified human RAGE proteins were 360 nM for Gcer-AGE and 1.35 microM for Gcol-AGE. The radiolabeled-ligand binding assay with RAGE-expressing COS-7 cells revealed similar association kinetics. Competitive SPR assay with antibodies specific to the respective AGE fractions demonstrated abundant existence of both Gcer- and Gcol-AGE in RAGE affinity-purified proteins from human sera. The serum contents of Gcer- and Gcol-AGE in a diabetic patient were about twice as high as those in a healthy control. Functionally, Gcer- and Gcol-AGE upregulated the endothelial cell levels of mRNA for vascular endothelial growth factor (VEGF) and the secretion of its protein product into the culture media and DNA synthesis in a dose-dependent manner. Further, these endothelial responses were augmented by RAGE overexpression. The results suggest that RAGE engagement of Gcer- and Gcol-AGE may elicit angiogenesis through the induction of autocrine VEGF, thereby contributing to the development and progression of diabetic angiopathies.
- Subjects :
- DNA Replication
Umbilical Veins
medicine.medical_specialty
Endothelium
Angiogenesis
Endocrinology, Diabetes and Metabolism
Receptor for Advanced Glycation End Products
Ligands
Cell Line
RAGE (receptor)
chemistry.chemical_compound
Endocrinology
Internal medicine
Chlorocebus aethiops
Internal Medicine
medicine
Animals
Humans
RNA, Messenger
Receptors, Immunologic
Autocrine signalling
Cells, Cultured
Aldehydes
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Haplorhini
General Medicine
Surface Plasmon Resonance
Vascular endothelial growth factor
Endothelial stem cell
medicine.anatomical_structure
chemistry
Cell culture
COS Cells
3-Deoxyglucosone
Endothelium, Vascular
business
Subjects
Details
- ISSN :
- 01688227
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Diabetes Research and Clinical Practice
- Accession number :
- edsair.doi.dedup.....2d79aa3277f507672836af2f0eaf9ee8