Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction.
Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological demonstration of the presence of AGE proteins in several human tissues suggests that they may be involved in aging, diabetic complications and atherosclerosis. AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we examined whether MSR could mediate the endocytic uptake of AGE proteins by using Chinese hamster ovary (CHO) cells overexpressing bovine type II MSR (CHO-SRII). 125I-labelled AGE bovine serum albumin (125I-AGE-BSA) as well as 125I-acetylated low-density lipoprotein (125I-acetyl-LDL) underwent endocytic degradation by CHO-SRII cells, but not by control CHO cells. Endocytic degradation of 125I-acetyl-LDL and 125I-AGE-BSA by CHO-SRII cells was significantly inhibited by unlabeled AGE-BSA, as well as by acetyl-LDL. Immunoelectron microscopic studies using both AGE-BSA conjugated with gold particles and anti-(bovine MSR) antibody (D2) revealed co-localization of gold particles and the reactive sites for the antibody at coated pits of plasma membranes as well as in endosomes. These results clearly show that MSR mediates the endocytic uptake and degradation of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.
Araki
N
N
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Higashi
T
T
Mori
T
T
Shibayama
R
R
Kawabe
Y
Y
Kodama
T
T
Takahashi
K
K
Shichiri
M
M
Horiuchi
S
S
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D004705:Endocytosis; D005947:Glucose / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism; D015416:Maillard Reaction; D016253:Microscopy, Immunoelectron; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D012710:Serum Albumin, Bovine / Q000378:metabolism
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C032629:acetyl-LDL; D012710:Serum Albumin, Bovine; D005947:Glucose