| RRC ID |
41356
|
| 著者 |
Ohgami N, Nagai R, Miyazaki A, Ikemoto M, Arai H, Horiuchi S, Nakayama H.
|
| タイトル |
Scavenger receptor class B type I-mediated reverse cholesterol transport is inhibited by advanced glycation end products.
|
| ジャーナル |
J Biol Chem
|
| 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). (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.
|
| 巻・号 |
276(16)
|
| ページ |
13348-55
|
| 公開日 |
2001-4-20
|
| DOI |
10.1074/jbc.M011613200
|
| PII |
S0021-9258(19)34460-6
|
| PMID |
11278947
|
| MeSH |
Animals
Binding, Competitive
CD36 Antigens / genetics
CD36 Antigens / physiology*
CHO Cells
Cholesterol / metabolism*
Cricetinae
Endocytosis / drug effects
Endocytosis / physiology*
Glycation End Products, Advanced / pharmacokinetics*
Iodine Radioisotopes / pharmacokinetics
Kinetics
Lipoproteins, HDL / metabolism
Lipoproteins, LDL / pharmacology
Liver / cytology
Liver / metabolism*
Male
Membrane Proteins*
Rats
Rats, Wistar
Receptors, Immunologic*
Receptors, Lipoprotein / physiology
Receptors, Scavenger
Recombinant Proteins / metabolism
Scavenger Receptors, Class A
Scavenger Receptors, Class B
Serum Albumin, Bovine / pharmacokinetics*
|
| IF |
4.238
|
| 引用数 |
122
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
CHO-K1(RCB0285)
Hep G2(RCB0459) |
