Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins.
Long term incubation of proteins with glucose, named the Maillard reaction (Maillard, L. C. (1912) C. R. Acad. Sci. (Paris) 154, 66-68), gives rise to advanced glycosylation end product (AGE) with fluorescence, color, as well as cross-linked properties. The receptor-mediated endocytosis of AGE-proteins by macrophages was reported (Vlassara, H., Brownlee, M., and Cerami, A. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5588-5592). The present study on the binding of AGE-bovine serum albumin (BSA) to rat peritoneal macrophages and sinusoidal liver cells demonstrated the presence of a saturable, high affinity receptor for AGE-BSA with Kd = 2.4 x 10(-7) M (macrophages) and 2.1 x 10(-7) M (sinusoidal cells). The cellular binding of AGE-BSA and its endocytic uptake by these cells were competitively inhibited by BSA preparations modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, ligands known to be specific for a scavenger receptor for aldehyde-modified proteins (Horiuchi, S., Murakami, M., Takata, K., and Morino, Y. (1986). J. Biol. Chem. 261, 4962-4966). These ligands also had a profound in vivo effect on the plasma clearance of 125I-AGE-BSA as well as its hepatic uptake. Thus, endocytic uptake of AGE-proteins by macrophages appeared to be mediated by a scavenger receptor for aldehyde-modified proteins. This provides evidence for the biological importance of the scavenger receptor in eliminating senescent macromolecules from the circulation.
Takata
K
K
Department of Biochemistry, Kumamoto University Medical School, Japan.
Horiuchi
S
S
Araki
N
N
Shiga
M
M
Saitoh
M
M
Morino
Y
Y
D000818:Animals; D001667:Binding, Competitive; D004705:Endocytosis; D005557:Formaldehyde / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism*
D006023:Glycoproteins; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface; C044105:formaldehyde-serum albumin; C044106:formaldehyde-serum albumin receptor; D005557:Formaldehyde; D012710:Serum Albumin, Bovine