title: FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products.
abstract: 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), cell surface glycoprotein CD36, scavenger receptor class B type I (SR-BI), and lectin-like oxidized low density lipoprotein receptor-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 have recently isolated from a cDNA library prepared from human umbilical vein endothelial cells, such as the scavenger receptor expressed by endothelial cells-I (SREC-I); the fasciclin EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1 (FEEL-1); and its paralogous protein, FEEL-2. At 4 degrees C, (125)I-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 K(d) of 2.55 and 1.68 microg/ml, respectively, but not to CHO cells expressing SREC (CHO-SREC) and parent CHO cells. At 37 degrees C, (125)I-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 a prerequisite to bind AGEs. The (125)I-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.
authors.affiliation: Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hideki
authors.initials: H
authors.lastname: Adachi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tomita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D000368:Aged; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001692:Biological Transport; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D004705:Endocytosis / Q000502:physiology*; D004730:Endothelium, Vascular; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D014162:Transfection; D014471:Umbilical Veins
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; C449926:STAB1 protein, human; C449927:STAB2 protein, human; C486732:Stab1 protein, mouse; C486733:Stab2 protein, mouse; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine