CD36, a Member of the Class B Scavenger Receptor Family, as a Receptor for Advanced Glycation End Products

Nobutaka Ohgami, Ryoji Nagai, Mamoru Ikemoto, Hiroyuki Arai, Akihiko Kuniyasu, Seikoh Horiuchi, Hitoshi Nakayama

Research output: Contribution to journalArticlepeer-review

207 Citations (Scopus)

Abstract

Interaction of advanced glycation end products (AGE) with AGE receptors induces several cellular phenomena potentially relating to diabetic complications. Five AGE receptors identified so far are RAGE (receptor for AGE), galectin-3, 80K-H, OST-48, and SRA (macrophage scavenger receptor class A types I and II). Since SRA 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, although belonging to the class B scavenger receptor family, can recognize AGE proteins as ligands. This was tested at the cellular level in this study using Chinese hamster ovary (CHO) cells overexpressing human CD36 (CD36-CHO cells). Cellular expression of CD36 was confirmed by immunoblotting and immunofluorescent microscopy using anti-CD36 antibody. Upon incubation at 37 °C, 125I-AGE-bovine serum albumin (AGE-BSA) and 125I-oxidized low density lipoprotein (LDL), an authentic ligand for CD36, were endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CD36-CHO cells, but not wild-type CHO cells. In binding experiments at 4 °C, 125I-AGE-BSA exhibited specific and saturable binding to CD36-CHO cells (Kd = 5.6 μg/ml). The endocytic uptake of 125I-AGE-BSA by these cells was inhibited by 50% by oxidized LDL and by 60% by FA6-152, an anti-CD36 antibody inhibiting cellular binding of oxidized LDL. Our results indicate that CD36 expressed by these cells mediates the endocytic uptake and subsequent intracellular degradation of AGE proteins. Since CD36 is one of the major oxidized LDL receptors and is up-regulated in macrophage- and smooth muscle cell-derived foam cells in human atherosclerotic lesions, these results suggest that, like oxidized LDL, AGE proteins generated in situ are recognized by CD36, which might contribute to the pathogenesis of diabetic macrovascular complications.

Original languageEnglish
Pages (from-to)3195-3202
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number5
DOIs
Publication statusPublished - 02-02-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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