Scavenger receptor class B type I-mediated reverse cholesterol transport is inhibited by advanced glycation end products.
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). (125)I-AGE-bovine serum albumin (AGE-BSA) was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CHO-SR-BI cells. (125)I-AGE-BSA exhibited saturable binding to CHO-SR-BI cells (K(d) = 8.3 microg/ml). Endocytic uptake of (125)I-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 (IC(50) <10 microg/ml). Furthermore, AGE-BSA partially inhibited (by <30%) the selective uptake of HDL-CE in human hepatocarcinoma HepG2 cells (IC(50) <30 microg/ml). In addition, [(3)H]cholesterol efflux from CHO-SR-BI cells to HDL was significantly inhibited by AGE-BSA in a dose-dependent manner (IC(50) <30 microg/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.
Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Ohe-Honmachi, Kumamoto 862-0973, Japan.
N
N
Ohgami
R
R
Nagai
A
A
Miyazaki
M
M
Ikemoto
H
H
Arai
S
S
Horiuchi
H
H
Nakayama
D000818:Animals; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000502:physiology; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D018955:CD36 Antigens; D017127:Glycation End Products, Advanced; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; C081628:advanced glycation end products-bovine serum albumin; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine; D002784:Cholesterol