http://morelife.org/references/full_papers/14568010.pdf

Novel inhibitors of advanced glycation endproducts

Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD.

The incidence of diabetes, especially type 2 diabetes, is increasing at an alarming rate assuming epidemic proportions (1). Worldwide, 124 million people had diabetes by 1997, although an estimated 221 million people will have diabetes by the year 2010 (1).

https://care.diabetesjournals.org/content/diacare/29/6/1420.full.pdf

Diabetes and Advanced Glycoxidation End-Products

Cd36, a member of the class b scavenger receptor family, as a receptor for advanced glycation end products.

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 macro-phage 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.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.0408h.x

Macrophage Scavenger Receptor Mediates the Endocytic Uptake and Degradation of Advanced Glycation End Products of the Maillard Reaction

In patients with diabetic renal failure plasma advanced glycosylation end-products (AGE) levels are reported to be elevated and dialyzer of continuous ambulatory peritoneal dialysis (CAPD) is usually used with a high glucose concentration. Here, an immunohistochemical study on human AGE accumulation in vascular beds and peritonea of patients with chronic renal failure (CRF) or those on CAPD was undertaken. Further, the influence of aging was studied using AGE-specific monoclonal antibody. 1. AGE accumulation was observed in radial arterial walls (from vascular intima to smooth muscle layer) of diabetic patients with CRF. Even in some non-diabetic patients with CRF (n = 3/6), especially in those with a long history of CRF and dialysis treatment, similar positive staining was seen in vascular walls. No AGE staining was observed in any renal tissue of age-matched control subjects including tissue from patients with acute renal failure. 2. Although AGE accumulation was not seen in the peritonea of CRF patients with no prior CAPD therapy, it was seen in the mesothelial layers and in adjacent coarse connective tissues of peritonea from patients on CAPD (n = 6), even from as early as only 3 months of CAPD therapy. 3. AGE accumulation was observed in the vascular bed of the non-diabetic aged kidney with normal function, but not in that of the young kidney. Thus, AGE accumulation in the vascular bed may depend on the degree and term of renal impairment and on aging in addition to diabetes. AGE accumulation in the peritonea became positive following CAPD treatment, indicating that it might affect the efficiency of CAPD.

N. Mimura

Papers

Immunohistochemical study of human advanced glycosylation end products (AGE) in chronic renal failure.