Scavenger Receptor Class B Type I-mediated Reverse Cholesterol Transport Is Inhibited by Advanced Glycation End Products

Nobutaka Ohgami, Ryoji Nagai, Akira Miyazaki, Mamoru Ikemoto, Hiroyuki Arai, Seikoh Horiuchi, Hitoshi Nakayama

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)

Abstract

Cellular interactions of advanced glycation end products (AGE) are mediated by AGE receptors. We demonstrated previously that class A scavenger receptor types I and II (SR-A) and CD36, a member of class B scavenger receptor family, serve as the AGE receptors. In this study, we investigated whether scavenger receptor class B type I (SR-BI), another receptor belonging to class B scavenger receptor family, was also an AGE receptor. We used Chinese hamster ovary (CHO) cells overexpressed hamster SR-BI (CHO-SR-BI cells). 125I-AGE-bovine serum albumin (AGE-BSA) was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CHO-SR-BI cells. 125I-AGE-BSA exhibited saturable binding to CHO-SR-BI cells (K d = 8.3 μg/ml). Endocytic uptake of 125I-AGE-BSA by CHO-SR-BI cells was completely inhibited by oxidized low density lipoprotein (LDL) and acetylated LDL, whereas LDL exerted only a weak inhibitory effect (<20%). Cross-competition experiments showed that AGE-BSA had no effect on HDL binding to these cells and vice versa. Interestingly, however, SR-BI-mediated selective uptake of HDL-CE was completely inhibited by AGE-BSA in a dose-dependent manner (IC50 <10 μg/ml). Furthermore, AGE-BSA partially inhibited (by <30%) the selective uptake of HDL-CE in human hepatocarcinoma HepG2 cells (IC50 <30 μg/ml). In addition, [3H]cholesterol efflux from CHO-SR-BI cells to HDL was significantly inhibited by AGE-BSA in a dose-dependent manner (IC50 <30 μg/ml). Our results indicate that AGE proteins, as ligands for SR-BI, effectively inhibit both SR-BI-mediated selective uptake of HDL-CE and cholesterol efflux from peripheral cells to HDL, suggesting that AGE proteins might modulate SR-BI-mediated cholesterol metabolism in vivo.

Original languageEnglish
Pages (from-to)13348-13355
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number16
DOIs
Publication statusPublished - 20-04-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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