RAGE - A NOVEL CELLULAR RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS

Exposure of proteins to reducing sugars results in nonenzymatic glycat ion with the ultimate formation of advanced glycation end products (AG Es). One means through which AGEs modulate cellular functions is throu gh binding to specific cell surface acceptor molecules. The receptor f or AGEs (RAGE) is such a receptor and is a newly identified member of the immunoglobulin superfamily expressed on endothelial cells (ECs), m ononuclear phagocytes (MPs), and vascular smooth muscle cells (SMCs) i n both vivo and in vitro. Binding of AGEs to RAGE results in induction of cellular oxidant stress, as exemplified by the generation of thiob arbituric acid-reactive substances, expression of heme oxygenase type I, and activation of the transcription factor NF-kB, with consequences for a range of cellular functions, AGEs on the surface of diabetic re d cells enhance binding to endothelial RAGE and result in enhanced oxi dant stress in the vessel wall. By using reagents to selectively block access to RAGE, the role of this receptor in AGE-mediated perturbatio n of cellular properties can be dissected in detail.