title: CD36, serves as a receptor for advanced glycation endproducts (AGE).
abstract: Interaction of advanced glycation endproducts (AGE) with AGE receptors induces several cellular phenomena relating potentially to diabetic complications. Five AGE receptors identified so far are receptor for AGE (RAGE), 80 K-H, OST-48, galectin-3, and macrophage scavenger receptor, types I and II (SR-A) [Eur. J. Biochem. 230 (1995) 408; Nature 386 (1997) 292.]. Since SR-A is known to belong to the class A scavenger receptor family and the scavenger receptor collectively represents a family of multiligand lipoprotein receptors, it is possible that CD36 belonging to class B scavenger receptor family (SR-B) can recognize AGE proteins as a ligand. This was tested in the present study at the cellular level by using Chinese hamster ovary (CHO) cells overexpressing human CD36 (CHO-CD36 cells). 125I-AGE-bovine serum albumin (BSA) was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CHO-CD36, but not wild-type CHO cells. Endocytic uptake of 125I-AGE-BSA by these cells was inhibited 50% by oxidized low-density lipoprotein (Ox-LDL) and 60% by FA6-152, an anti-CD36 antibody inhibiting cellular binding of Ox-LDL. Our results indicate that CD36 expressed by these cells mediates endocytic uptake and subsequent intracellular degradation of AGE proteins. Since CD36 is one of the major Ox-LDL receptors and is up-regulated in macrophage- and smooth muscle cell-derived foam cells in human atherosclerotic lesions, the present results suggest that, like Ox-LDL, AGE proteins generated in situ are recognized by CD36, which might contribute to the pathogenesis of diabetic macrovascular complications.
authors.affiliation: Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Ohe-Honmachi, 862-0973, Kumamoto, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ikemoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Hakamata
authors.forename: Seikoh
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D004705:Endocytosis; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014162:Transfection
chemical_list: D018955:CD36 Antigens; D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B