Advanced glycation end products (AGE) inhibit scavenger receptor class B type I-mediated reverse cholesterol transport: a new crossroad of AGE to cholesterol metabolism.
Advanced glycation end products (AGE) -modified proteins behave as active ligands for several receptors belonging to the scavenger receptor family. Scavenger receptor class B type I (SR-BI) was identified as the first high density lipoprotein (HDL) receptor that mediates selective uptake of HDL-cholesteryl esters (HDL-CE). This study investigated whether AGE proteins serve as ligands for SR-BI and affect SR-BI-mediated cholesterol transport using Chinese hamster ovary (CHO) cells overexpressing hamster SR-BI (CHO-SR-BI cells). [125I] AGE-bovine serum albumin (AGE-BSA) underwent active endocytosis and subsequent lysosomal degradation by CHO-SR-BI cells, indicating that SR-BI serves as an AGE receptor. SR-BI-mediated selective uptake of HDL-CE by CHO-SR-BI cells was efficiently inhibited by AGE-BSA although AGE-BSA had no effect on HDL binding to CHO-SR-BI cells. In addition, AGE-BSA significantly inhibited the efflux of [3H] cholesterol from CHO-SR-BI cells to HDL. These findings suggest the possibility that AGE proteins in the circulation interfere with the functions of SR-BI in reverse cholesterol transport by inhibiting the selective uptake of HDL-CE, as well as cholesterol efflux from peripheral cells to HDL, thereby accelerating diabetes-induced atherosclerosis.
Ohgami
Nobutaka
N
Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. miya@med.showa-u.ac.jp
Miyazaki
Akira
A
Sakai
Masakazu
M
Kuniyasu
Akihiko
A
Nakayama
Hitoshi
H
Horiuchi
Seikoh
S
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018955:CD36 Antigens / Q000187:drug effects* / Q000378:metabolism; D016466:CHO Cells / Q000187:drug effects; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008565:Membrane Proteins; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D002788:Cholesterol Esters; D017127:Glycation End Products, Advanced; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol