Identification of pentosidine as a native structure for advanced glycation end products in beta-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis.
beta-2-Microglobulin (beta-2m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA). Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta-2m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta-2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in beta-2m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived beta-2m-containing amyloid fibrils to the pathogenesis of DRA.
Miyata
T
T
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Taneda
S
S
Kawai
R
R
Ueda
Y
Y
Horiuchi
S
S
Hara
M
M
Maeda
K
K
Monnier
V M
VM
D000682:Amyloid / Q000737:chemistry*; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000737:chemistry*
D000682:Amyloid; D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin; D001120:Arginine; C062187:pentosidine; D008239:Lysine