Molecular heterogeneity of amyloid β2-microglobulin and modification with advanced glycation end products

By using liquid chromatography-electrospray ionization mass spectrometry, Western blotting and N-terminal amino acid sequence analysis, we characterized the molecular heterogeneity and advanced glycation end product (AGE) modification of beta (2)-microglobulin (beta (2)m) extracted from the amyloid tissue of a hemodialysis patient. Amyloid plm was composed of full-length beta (2)m, truncated plm and dimer beta (2)m. Truncated plm and dimer plm were modified with AGEs such as imidazolone and N-epsilon-(carboxymethyl)lysine, and showed fluorescence characteristic of AGE. Truncated beta (2)m species were formed by cleavage between amino acid residues of Pro(6)/Ile(7), Gln(8)/Val(9) and Val(9)/Tyr(10). Heterogeneous dimer beta (2)m species showed the molecular masses of 22 591 and 23 675, which resulted from cross-linking between truncated beta (2)m. (C) 2001 Elsevier Science B.V. All rights reserved.