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Papers In Press, published online ahead of print December 6, 2002
Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498
Corresponding Author: ishibash{at}jichi.ac.jp
Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins which accumulate in vascular tissues in aging and diabetes. Receptors for AGEs include scavenger receptors which recognize acetylated low density lipoproteins (Ac-LDL), such as scavenger receptor class AI/AII (SR-A), CD36, scavenger receptor class B type I (SR-BI), and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). The broad ligand repertoire of these receptors as well as the diversity of the receptors for AGEs have prompted us to examine whether AGEs are also recognized by the novel scavenger receptors which we has recently isolated from a cDNA library prepared from human umbilical vein endothelial cells: the scavenger receptor expressed by endothelial cells (SREC) and the fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor-1 (FEEL-1), and its paralogous gene, FEEL-2. At 4°C, 125I-AGE-bovine serum albumin (BSA) exhibited high affinity specific binding to Chinese hamster ovary (CHO) cells overexpressing FEEL-1 (CHO-FEEL-1) and FEEL-2 (CHO-FEEL-2) with Kd of 2.55 and 1.68 mg/ml, respectively, but not to CHO cells expressing SREC (CHO-SREC) and parent CHO cells. At 37°C, 125I-AGE-BSA was taken up and degraded by CHO-FEEL-1 and CHO-FEEL-2 cells but not by CHO-SREC and parent CHO cells. Thus, the ability to bind Ac-LDL is not necessarily prerequisite for the ability to bind AGEs. The 125I-AGE-BSA binding to CHO-FEEL-1 and CHO-FEEL-2 cells was effectively inhibited by Ac-LDL and polyanionic SR-A inhibitors such as fucoidan, polyinosinic acids and dextran sulfate, but not by native LDL, oxidized LDL or HDL. FEEL-1, which is expressed by the liver and vascular tissues, may recognize AGEs, thereby contributing to the development of diabetic vascular complications and atherosclerosis.
J. Biol. Chem, 10.1074/jbc.M210211200
Submitted on October 4, 2002
Revised on December 2, 2002
Accepted on December 6, 2002
FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products
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