Thornalley Paul J [a].
Cell activation by glycated proteins. Age receptors, receptor recognition
factors and functional classification of AGEs, Cellular & Molecular Biology (Noisy-Le-Grand) 44(7) :1013-1023, 1998.
Abstract
Proteins modified by advanced glycation endproducts (AGE) bind to cell
surface receptors and other AGE binding proteins. AGE-binding receptors are:
scavenger receptors types I and II, the receptor for advanced glycation
endproducts (RAGE), oligosaccharyl transferase-48 (OST-48, AGE-R1), 80K-H
phosphoprotein (AGE-R2) and galectin-3 (AGE-R3). AGE receptors are found in
monocytes, macrophages, endothelial cells, pericytes, podocytes, astrocytes
and microglia. AGE-modified proteins also bind to lysozyme
and lactoferrin. A critical review of the evidence for receptors binding
AGE-modified protein binding in vivo is presented. Scavenger receptors have
only been shown to bind proteins modified by AGE to a much higher extent than
found in vivo. 80K-H phosphoprotein is involved in FGFR3 signal transduction
to MAP kinase, and may be involved in AGE-receptor signal transduction.
Whether all of these proteins bind AGE-modified proteins in vivo is not yet
clear. Cell activation in response to AGE-modified proteins is associated
with increased expression of extracellular matrix proteins, vascular adhesion
molecules, cytokines and growth factors. Depending on the cell type and
concurrent signaling, this is associated with chemotaxis,
angiogenesis, oxidative stress, cell proliferation or programmed cell death
(PCD). Receptor recognition factors for agonism at the AGE receptor have been
little studied but to date hydroimidazolones appear to be the most likely
candidates. Pharmacologic inhibition of AGE receptor-mediated cell
activation with specific antagonists may provide the basis for therapeutic
intervention in diseases where AGE accumulation is a suspected etiological
factor vascular complications of diabetes, macrovascular disease, renal
insufficiency and Alzheimer's disease.
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